Pancreatic acinar cell carcinoma is a rare malignant pancreatic neoplasm. To the best of our knowledge, there has been no report on spontaneous rupture of acinar cell carcinoma.
PRESENTATION OF CASE
A 39-year-old Azari male presented with a history of sudden onset, acute epigastric pain of 12-h duration. Eight hours later the patient's general condition rapidly deteriorated, blood pressure was decreased to 90/70 mm/Hg and heart rate was increased to 120 beat/min. Emergent abdominal computed tomography scan showed a well-defined hypo-dense, necrotic mass, measured 12 cm × 12 cm that was originating from the uncinate process of pancreas with marked free peritoneal fluid and extensive haziness of retroperitoneal and mesenteric fat compatible with marked bleeding. Emergent abdominal operation was performed and histopathology revealed acinar cell carcinoma of the pancreas.
Pancreatic acinar cell carcinoma (ACC) usually presents with abdominal pain, nausea and vomiting. To best of our knowledge, no report has been made of spontaneous rupture of ACC.
Pancreatic carcinoma may present as acute abdomen due to rupture of underlying neoplasm.
Acinar cell carcinoma; Pancrease; Rupture
While the rat pancreas is susceptible to experimental cancer induction, the spontaneous incidence of pancreatic cancer in this species is reported to be very low. However, we observed unusually high incidences of focal acinar hyperplasia and acinar adenoma in vehicle control male F344/N rats of some NCI/NTP 2-year toxicological studies. The vehicle in these studies was corn oil given by gavage. Focal acinar hyperplasia, acinar adenoma, and acinar carcinoma (found rarely) represent a continuous spectrum of proliferative lesions of the exocrine pancreas. While the carcinomas have clear morphological indications of malignancy, the biological behavior of focal acinar hyperplasia and acinar adenoma is not known. Although induction of acinar carcinomas is considered clear evidence of carcinogenicity of a test chemical, significantly increased incidences in treated rats of acinar adenomas but not carcinomas provides some evidence of carcinogenicity. The association of acinar hyperplasia and adenoma with vegetable oil gavage complicates the interpretation when marginally elevated incidences of these lesions are observed in rats administered the test chemical in vegetable oil vehicle. Studies of the biological behavior of exocrine pancreatic lesions in male rats would be helpful in assessing the significance of their presence when found after test compound administration.
The pathological features of 12 acinar cell neoplasms of the pancreas are described; these comprise 11 carcinomas, of which seven were pure acinar cell growths and four were mixed acinar and ductal carcinomas, and one adenoma. These tumors occurred in a series of 105 during the period 162-75. Thrombotic endocarditis developed in three out the 11 carcinoma cases. The distinctive histological features of these neoplasms and the means of differentiating them from anaplastic carcinomas and certain other carcinomas, for example, islet cell carcinoma, oat cell carcinomas, and carcinoid tumours, are discussed. The poor prognosis of pancreatic cancers is emphasized, and reasons are put forward for believing that future epidemiological studies may need to take account of the histological types of pancreatic carcinoma.
Acinar cell carcinoma of the pancreas is an uncommon malignancy, accounting for less than 1% of all pancreatic neoplasms. Because of its rarity, only a few retrospective studies are available to help guide management. We report the case of a patient with metastatic ACC who achieved prolonged survival as a result of personalized treatment designed in part on the basis of molecular and in-vitro data collected on analysis of the tumor and a cell line developed from the liver metastasis. To our knowledge, this represents the first human cell line of ACC. The molecular findings on this case and this patient's cell line may be of use in the management of future cases of this rare tumor and allow the identification of potential novel targets for the effective treatment of this disease.
acinar cell pancreatic cancer; prolonged survival; personalized medicine; cell line
Acinar cystic transformation of the pancreas is also known as acinar cell cystadenoma (ACC), and this is an extremely rare benign lesion that was first described in April 2002. We report here on a case of a previously asymptomatic patient with pancreatic ACC and this was diagnosed by computed tomography (CT) and magnetic resonance imaging (MRI). To the best of our knowledge, there is no previous report concerning the CT or MRI features of ACC in the medical literature. We present here the CT, MRI and pathological findings of pancreatic ACC.
Pancreatic acinar cell; Acinar cystadenoma; Neoplasms; Pancreatic cyst; Computed tomography (CT); Magnetic resonance imaging (MRI)
A case of pancreatic carcinoma with both acinar and endocrine features is presented. The patient was a 52-year-old female presenting with jaundice of 3 weeks' duration. The tumor was a 6 x 6 cm-sized round solid mass in the head of pancreas, invading the superior mesenteric vein. Histologically, it was composed of monotonous ovoid cells with eosinophilic granular cytoplasm in solid nests and sheets with occasional acinar and glandular differentiation. Immunohistochemical study revealed coexpression of acinar and endocrine markers; amylase, chromogranin, neuron-specific enolase, glucagon, somatostatin, and gastrin in tumor cells. This is the first documented case of mixed acinar-endocrine carcinoma of the pancreas in Korea, and its amphicrine nature reflects a close histogenetic relationship between pancreatic exocrine and endocrine cells.
A series of 40 consecutive cases of acinar cell carcinoma of the pancreas treated at Memorial Sloan-Kettering Cancer Center is presented, with an emphasis on evaluation of activity to new therapeutic agents.
Acinar cell carcinoma (ACC) of the pancreas is a rare neoplasm, accounting for 1% of all pancreatic neoplasms. There remains a lack of data regarding the use of systemic therapy in this disease. We present a series of 40 consecutive cases of ACC of the pancreas treated at Memorial Sloan-Kettering Cancer Center, with an emphasis on evaluation of activity of new therapeutic agents.
Patients reviewed at our institution from January 2000 through January 2011 were identified from an institutional database with prior institutional review board approval. Pathology was confirmed in all cases as ACC or a closely related entity.
Forty patients were identified; 29 were male (73%). The median age at diagnosis was 65 years (range, 16–87 years). The median overall survival (OS) time for patients with localized, resectable disease was 56.9 months and the OS time for patients with metastatic ACC (n = 18) was 19.6 months. Six patients with metastatic or recurrent ACC had a partial response to chemotherapy and five patients had stable disease for ≥6 months on systemic chemotherapy. Clinical observation was made of a patient with ACC and hereditary nonpolyposis colorectal cancer and a patient with ACC and a BRCA1 germline mutation.
ACC is moderately chemoresponsive to agents that have activity in pancreatic adenocarcinoma and colorectal carcinoma. A potential association between germline mutations in DNA mismatch repair genes and ACC warrants further evaluation.
Pancreas; Acinar; Genetics; BRCA
Acinar and ductal cells of the exocrine pancreas form a close functional unit. Although most studies contain data either on acinar or ductal cells, an increasing number of evidence highlights the importance of the pancreatic acinar-ductal functional unit. One of the best examples for this functional unit is the regulation of luminal pH by both cell types. Protons co-released during exocytosis from acini cause significant acidosis, whereas, bicarbonate secreted by ductal cells cause alkalization in the lumen. This suggests that the first and probably one of the most important role of bicarbonate secretion by pancreatic ductal cells is not only to neutralize the acid chyme entering into the duodenum from the stomach, but to neutralize acidic content secreted by acinar cells. To accomplish this role, it is more than likely that ductal cells have physiological sensing mechanisms which would allow them to regulate luminal pH. To date, four different classes of acid-sensing ion channels have been identified in the gastrointestinal tract (transient receptor potential ion channels, two-pore domain potassium channel, ionotropic purinoceptor and acid-sensing ion channel), however, none of these have been studied in pancreatic ductal cells. In this mini-review, we summarize our current knowledge of these channels and urge scientists to characterize ductal acid-sensing mechanisms and also to investigate the challenge of the acinar acid load on ductal cells.
pancreatic duct; bicarbonate
Acinar cell carcinoma (ACC) is a rare pancreatic tumour with a favourable prognosis compared with the more common ductal adenocarcinoma. The radiological findings of this tumour have been described in the literature; however, only limited data are available regarding the metastatic features of ACC of the liver, the most common metastatic site. We report a case of ACC of the pancreas with a hepatic metastasis from a benign-appearing malignant pancreatic lesion.
There is strong evidence that induced pancreatic adenomas and carcinomas derive from ductal and ductular cells in the pancreas. We base our beliefs on our knowledge of the embryology and histology of the pancreas in Syrian golden hamsters, along with the sequential alterations that occur during exocrine pancreatic tumor formation. This concept also has been supported by much experimental evidence, including autoradiographic, immunologic and in vitro studies. We also present other viewpoints on the origin of pancreatic cancer histogenesis and outline certain areas of disagreement. We report the development of acinar cell lesions under certain experimental dietary conditions in hamsters (the lesions resemble those commonly seen in the rat pancreatic tumor model) and the nature of these lesions.
Background & Aims
Mist1 is a basic helix-loop-helix (bHLH) transcription factor that is important to the proper development of the exocrine pancreas. The aim of this study was to investigate the role of Mist1 in modulating acinar cell proliferation.
Ductal and acinar pancreatic cell lines were engineered to express an inducible Mist1 cDNA or to express an shRNA that targeted endogenous Mist1. Alterations in RNA and protein levels were detected by real-time RT-PCR and immunoblots. Chromatin immunoprecipitation and reporter gene assays were performed to map Mist1-responsive elements on target genes; the overall proliferation index of acinar cells from Mist1 null pancreata was evaluated by immunohistochemistry.
Expression of Mist1 resulted in a significant decrease in the proliferative potential of cells that was associated with induced expression of p21CIP1/WAF1. shRNA-directed knock-down of p21CIP1/WAF1 generated cells that were refractory to Mist1 expression wheras knockdown of Mist1 transcripts or deletion of Mist1 from the mouse genome led to increased cell proliferation and a concomitant decrease in p21CIP1/WAF1 protein levels. Surprisingly, Mist1-dependent activation of the p21CIP1/WAF1 promoter was independent of classic bHLH protein binding sites. Instead, Sp1 binding sites were essential for Mist1-dependent transcription, suggesting that Mist1 activates p21CIP1/WAF1 expression through a unique Sp1 pathway. Indeed, coimmunoprecipitation studies demonstrated that Mist1 and Sp1 were found within the same transcription complex.
Our results show that Mist1 has a dual role in the development of the exocrine pancreas - controlling cell proliferation and promoting terminal differentiation.
Alcohol abuse is a major cause of pancreatitis, a condition that can manifest as both acute necroinflammation and chronic damage (acinar atrophy and fibrosis). Pancreatic acinar cells can metabolize ethanol via the oxidative pathway, which generates acetaldehyde and involves the enzymes alcohol dehydrogenase and possibly cytochrome P4502E1. Additionally, ethanol can be metabolized via a nonoxidative pathway involving fatty acid ethyl ester synthases. Metabolism of ethanol by acinar and other pancreatic cells and the consequent generation of toxic metabolites, are postulated to play an important role in the development of alcohol-related acute and chronic pancreatic injury. This current work will review some recent advances in the knowledge about ethanol actions on the exocrine pancreas and its relationship to inflammatory disease and cancer.
Pancreas; Calcium; Ethanol; Reactive oxygen species; Pancreatitis
Pancreatic carcinogenesis in the Syrian hamster, induced by beta-oxidized derivatives of N-nitroso-di-n-propylamine, constitutes a valuable model of human cancer of the exocrine pancreas. In both species the majority of tumors are adenocarcinomas: superficially, on the basis of their histological appearance, these appear to be ductal in origin. However, sequential analysis, by electron microscopy, of the development of pancreatic neoplasia in the hamster model indicates that acinar cells may participate in the histogenesis of "ductal" adenomas and carcinomas. Acinar cells appear to undergo changes in differentiation, including pseudoductular transformation, giving rise to a new population of cells that resemble ductular or centroacinar types. This new population may then proliferate to form, first, cystic foci and subsequently cystadenomas and adenocarcinomas. Mucous metaplasia appears to develop at late stages of tumor development. Although the participation of ductular and centroacinar cells in pancreatic carcinogenesis cannot be excluded, very few tumors arise from the ductal epithelium. It is possible that some human pancreatic adenocarcinomas may also have their origin from dysplastic acinar cells, by analogy with the hamster model: focal acinar dysplasia being common in human pancreatic cancer patients.
Cellular plasticity in adult organs is involved in both regeneration and carcinogenesis. WT mouse acinar cells rapidly regenerate following injury that mimics acute pancreatitis, a process characterized by transient reactivation of pathways involved in embryonic pancreatic development. In contrast, such injury promotes the development of pancreatic ductal adenocarcinoma (PDA) precursor lesions in mice expressing a constitutively active form of the GTPase, Kras, in the exocrine pancreas. The molecular environment that mediates acinar regeneration versus the development of PDA precursor lesions is poorly understood. Here, we used genetically engineered mice to demonstrate that mutant Kras promotes acinar-to-ductal metaplasia (ADM) and pancreatic cancer precursor lesion formation by blocking acinar regeneration following acute pancreatitis. Our results indicate that β-catenin is required for efficient acinar regeneration. In addition, canonical β-catenin signaling, a pathway known to regulate embryonic acinar development, is activated following acute pancreatitis. This regeneration-associated activation of β-catenin signaling was not observed during the initiation of Kras-induced acinar-to-ductal reprogramming. Furthermore, stabilized β-catenin signaling antagonized the ability of Kras to reprogram acini into PDA preneoplastic precursors. Therefore, these results suggest that β-catenin signaling is a critical determinant of acinar plasticity and that it is inhibited during Kras-induced fate decisions that specify PDA precursors, highlighting the importance of temporal regulation of embryonic signaling pathways in the development of neoplastic cell fates.
Hypothesis: Bile and pancreatic juice exclusion from gut activates acinar stress kinases and exacerbates gallstone pancreatitis as evidenced by ameliorating effects of replacement therapy in an experimental model of duct ligation-induced acute pancreatitis. In early stages of gallstone pancreatitis, bile-pancreatic juice cannot enter the gut. Enteral exclusion worsens pancreatitis by causing feedback hyperstimulation of the exocrine pancreas that activates acinar cell stress kinases. Investigations using a unique surgical model, the Donor Rat Model, showed that duodenal replacement of bile-pancreatic juice in rats with duct ligation attenuates pancreatic stress kinase activation, reduces pancreatic cytokine production, and ameliorates pancreatic morphologic changes. These findings suggest that exclusion-induced acinar hyperstimulation, in the presence of duct obstruction, exacerbates acute pancreatitis via stress kinase activation. Although acinar hyperstimulation has often been implicated in acute pancreatitis pathogenesis, the lack of supporting evidence remains a conspicuous lacuna. The proposed hypothesis draws on fresh evidence to present a new paradigm that re-examines the role of exocrine pancreatic hyperstimulation in gallstone pancreatitis pathogenesis.
Foetal acinar components associated with the development of the hamster pancreas have been previously defined with the aid of an antifoetal pancreas serum. In immunohistology this antiserum also stained malignant ductal cells in N-nitrobis (2-oxopropyl) amine (BOP)-induced pancreatic adenocarcinoma. It did not stain adult pancreas structures including acini, ducts and islets of Langerhans. In this study, re-expression of foetal acinar antigens was disclosed before formation of tumours. Adenocarcinomas were not detected by conventional histology before the 24th week following initiation of the chemical treatment. However, staining with the antiserum was observed from the 7th week appearing in the apex of some acini cells having an almost normal histological appearance. Later, foetal acinar expression was frequently associated with evident morphological alterations in acini like dyskaryosis, enlarged cytoplasm or lumina. Staining of ducts with marked atypical epithelium and (as already reported) of neoplastic ducts was also observed. It was not detected in other pancreatic lesions viz. cystadenomas, mucoid glands and regular hyperplastic ducts. Acinar dedifferentiation as assessed by expression of foetal components preceded formation of tumours in all instances.
Breast glands and salivary glands are tubulo-acinar exocrine glands that can manifest as tumours with similar morphological features, but that differ in incidence and clinical behaviour depending on whether they are primary in breast or salivary glands. Salivary gland-like tumours of the breast are of two types: tumours with myoepithelial differentiation and those devoid of myoepithelial differentiation. The first and more numerous group comprises a spectrum of lesions ranging from “bona fide” benign (such as benign myoepithelioma and pleomorphic adenoma), to low grade malignant (such as adenoid cystic carcinoma, low grade adenosquamous carcinoma, and adenomyoepithelioma), to high grade malignant lesions (malignant myoepithelioma). The second group comprises lesions that have only recently been recognised, such as acinic cell carcinoma, oncocytic carcinoma of the breast, and the rare mucoepidermoid carcinoma.
myoepithelioma; malignant myoepithelioma; pleomorphic adenoma; low grade adenosquamous carcinoma; acinic cell carcinoma
Animal models of carcinoma of the pancreas provide new information regarding the pathways for histogenesis of the tumors. Four models, induced by chemical carcinogens or transgenic methods, are reviewed briefly from this perspective. Recent reports indicate that carcinomas with a ductal phenotype can arise from transformed acinar cells in rodents. A transgenic mouse model provides evidence that anaplastic carcinomas and islet cell tumors may arise from primitive cells that express the elastase gene, yet retain the potential to differentiate as islet cells. In a nitrosamine-induced hamster model, ductal carcinomas appear to arise directly from ductal cells. Carcinomas in this model contained mutations in the c-K-ras oncogene that are similar to those reported in about 75 percent of human pancreatic carcinomas, whereas acinar cell carcinomas of rats lacked this mutation. The histologic type of a carcinoma may reflect the cell of origin, but this statement is not always true. Therefore, classification of tumors on the basis of phenotype rather than on the presumed cell of origin is recommended. Among the animal models, the carcinomas in hamster pancreas rank as most similar to human pancreatic ductal adenocarcinomas in regard to the phenotype of the tumors and the prevalence of the c-K-ras mutation.
Background & Aims
Progression of diseases of the exocrine pancreas, which include pancreatitis and cancer, is associated with increased levels of cell stress. Pancreatic acinar cells are involved in development of these diseases and, because of their high level of protein output, they require an efficient, unfolded protein response (UPR), which mediates recovery from endoplasmic reticulum (ER) stress following the accumulation of misfolded proteins.
To study recovery from ER stress in the exocrine organ, we generated mice with conditional disruption of Xbp1 (a principle component of the UPR) in most adult pancreatic acinar cells (Xbp1fl/fl). We monitored the effects of constitutive ER stress in the exocrine pancreas of these mice.
Xbp1-null acinar cells underwent extensive apoptosis, followed by a rapid phase of recovery in the pancreas that included expansion of the centroacinar cell compartment, formation of tubular complexes that contained Hes1- and Sox9-expressing cells, and regeneration of acinar cells that expressed Mist1 from the residual, surviving Xbp1+ cell population.
XBP1 appears to be required for homeostatisis of acinar cells in mice; ER stress induces a regenerative response in the pancreas that involves acinar and centroacinar cells and promotes organ recovery from exocrine pancreas disease.
endoplasmic reticulum stress; pancreatic progenitor cells; protein folding; tissue regeneration
Purpose of review
This review focuses on studies from the past year that have greatly advanced our understanding of molecular and cellular regulation of pancreatic acinar cell function.
Recent advances focus on signals dictating pancreatic development, acinar cell fate, pancreatic growth, and secretion. Regeneration of acinar cells after pancreatitis depends on expression of embryonic signals in mature acinar cells. In this setting, acinar cells can also transdifferentiate into adipose cells. With the forced induction of certain early and endocrine-driving transcription factors, acinar cells can also transdifferentiate into β-cells. There has also been an increased understanding of acinar-to-ductal metaplasia and the subsequent formation of pancreatic intraepithelial neoplasia lesions. Multiple proteins involved in secretion have been characterized, including small guanosine triphosphate-binding proteins, soluble N-ethylmaleimide-sensitive factor attachment proteins, and ion channels.
These findings demonstrate the regenerative potential of the acinar cell to mitigate injurious states such as pancreatitis. The ability of acinar cells to transdifferentiate into β-cells could potentially provide a treatment for diabetes. Finally, the results might be helpful in preventing malignant transformation events arising from the acinar cell. Developments in proteomics and computer modeling could expand our view of proteins mediating acinar cell function.
calcium signaling; growth; regeneration; secretion; transdifferentiation
Pancreatic ductal adenocarcinoma is believed to arise from precursor lesions termed pancreatic intraepithelial neoplasia (PanIN). Mouse models have demonstrated that targeted expression of activated K-ras to mature acinar cells in the pancreas induces the spontaneous development of PanIN lesions; implying acinar-to-ductal metaplasia (ADM) is a key event in this process. Recent studies suggest Notch signaling is a key regulator of ADM. To assess if Notch1 is required for K-ras driven ADM we employed both an in vivo mouse model and in vitro explant culture system, in which an oncogenic allele of K-ras is activated and Notch1 is deleted simultaneously in acinar cells. Our results demonstrate that oncogenic K-ras is sufficient to drive ADM both in vitro and in vivo but that loss of Notch1 has a minimal effect on this process. Interestingly, while loss of Notch1 in vivo does not affect the severity of PanIN lesions observed, the overall numbers of lesions were greater in mice with deleted Notch1. This suggests Notch1 deletion renders acinar cells more susceptible to formation of K-ras-induced PanINs.
The elastase I (EI) gene is expressed at high levels in the exocrine pancreas and at lower levels in other regions of the gut. The transcriptional enhancer of the EI gene, from nucleotides -205 to -72, recapitulates the expression of the endogenous gene in transgenic mice; it directs not only pancreatic acinar cell expression of a human growth hormone (hGH) transgene but also expression to the stomach, duodenum, and colon. This pattern of selective expression limited to the gastroenteropancreatic organ system is specified by the A element, one of three functional elements in the EI enhancer. When multimerized, the A element directed expression of a hGH reporter gene selectively to the pancreas, stomach, and intestine in transgenic mice. Immunofluorescent localization of hGH indicated that the A element multimer transgenes were expressed in the acinar cells of the pancreas as well as in Brunner's gland cells of the duodenum. The A element binds a pancreatic acinar cell-specific factor, PTF1. Our results show that while the A element is responsible for directing tissue and cell type specificity, other elements of the enhancer must be involved in the regulation of the level of gene expression.
Background & Aims
Acinar cells constitute 90% of the pancreas epithelium, are polarized, and secrete digestive enzymes. These cells play a crucial role in pancreatitis and pancreatic cancer. However, there are no models to study normal acinar cell differentiation in vitro. The aim of this work was to generate and characterize purified populations of pancreatic acinar cells from embryonic stem cells (ES).
Reporter ES cells (Ela-pur) were generated that stably expressed both beta-galactosidase and puromycin resistance genes under the control of the elastase I promoter. Directed differentiation was achieved by incubation with conditioned media (CM) of cultured foetal pancreatic rudiments and adenoviral-mediated co-expression of p48/Ptf1a and Mist1, two bHLH transcription factors crucial for normal pancreatic acinar development and differentiation.
Selected cells expressed multiple markers of acinar cells, including digestive enzymes and proteins of the secretory pathway, indicating activation of a coordinated differentiation program. The genes coding for digestive enzymes were not regulated as a single module, thus recapitulating what occurs during in vivo pancreatic development. The generated cells displayed transient agonist-induced Ca2+ mobilization and exhibited a typical response to physiologic concentrations of secretagogues, including enzyme synthesis and secretion. Importantly, these effects did not imply the acquisition of a mixed acinar-ductal phenotype.
These studies allow for the first time to generate almost pure acinar-like cells from ES cells. This is the first normal cell-based model allowing the study of the acinar differentiation program in vitro.
Background & Aims
The mature pancreatic acinar cell is dedicated to the production of very large amounts of digestive enzymes. The early stages of pancreatic development require the Rbpj-form of the trimeric transcription factor complex PTF1 (PTF1-J). As acinar development commences, Rbpjl gradually replaces Rbpj; in the mature pancreas, PTF1 contains Rbpjl (PTF1-L). We investigated whether PTF1-L controls the expression of genes that complete the final stage of acinar differentiation.
We analyzed acinar development and transcription in mice with disrupted Rbpjl (Rbpjlko/ko mice). We performed comprehensive analyses of the mRNA population and PTF1 target genes in pancreatic acinar cells from these and wild-type mice.
In Rbpjlko/ko mice, acinar differentiation was incomplete and characterized by decreased expression (as much as 99%) of genes that encode digestive enzymes or proteins of regulated exocytosis and mitochondrial metabolism. Whereas PTF1-L bound regulatory sites of genes in normal adult pancreatic cells, the embryonic form (PTF1-J) persisted in the absence of Rbpjl and replaced PTF1-L; the extent of replacement determined gene expression levels. Loss of PTF1-L reduced expression (>2-fold) of only about 50 genes, 90% of which were direct targets of PTF1-L. The magnitude of the effects on individual digestive enzyme genes correlated with the developmental timing of gene activation. Absence of Rbpjl increased pancreatic expression of liver-restricted mRNAs.
Replacement of Rbpj by Rbpjl in the PTF1 complex drives acinar differentiation by maximizing secretory protein synthesis, stimulating mitochondrial metabolism and cytoplasmic creatine-phosphate energy stores, completing the packaging and secretory apparatus, and maintaining acinar-cell homeostasis.
Ptf1a; transdifferentiation; ChIP-Seq; RNA-Seq
The concept of pancreatic cancer origin is controversial. Acinar, ductal or islet cells have been hypothesized as the cell of origin. The pros and cons of each of these hypotheses are discussed. Based on the world literature and recent observations, pancreatic cells seem to have potential for phenotypical transdifferentiation, i.e ductal-islet, ductal-acinar, acinar-ductal, acinar-islet, islet-acinar and islet-ductal cells. Although the possibility is discussed that cancer may arise from either islet, ductal or acinar cells, the circumstances favoring the islet cells as the tumor cell origin include their greater transdifferentiation potency into both pancreatic and extrapancreatic cells, the presence of a variety of carcinogen-metabolizing enzymes, some of which are present exclusively in islet cells and the growth factor-rich environment of islets.