PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-5 (5)
 

Clipboard (0)
None

Select a Filter Below

Journals
Year of Publication
Document Types
1.  Endothelial cell junctional adhesion molecule C plays a key role in the development of tumors in a murine model of ovarian cancer 
The FASEB Journal  2013;27(10):4244-4253.
Junctional adhesion molecule C (JAM-C) is a transmembrane protein with significant roles in regulation of endothelial cell (EC) functions, including immune cell recruitment and angiogenesis. As these responses are important in promoting tumor growth, the role of EC JAM-C in tumor development was investigated using the ID8 syngeneic model of ovarian cancer. Within 10–15 wk, intraperitoneally injected ID8 cells form multiple tumor deposits and ascites that resemble human high-grade serous ovarian cancer. Compared to wild-type mice, survival in this model was increased in EC JAM-C knockouts (KOs; 88 vs. 96 d, P=0.04) and reduced in EC JAM-C transgenics (88 vs. 78.5 d, P=0.03), mice deficient in or overexpressing EC JAM-C, respectively. While tumor growth was significantly reduced in EC JAM-C KOs (87% inhibition at 10 wk, P<0.0005), this was not associated with alterations in tumor vessel density or immune cell infiltration. However, tumor microvessels from EC JAM-C-deficient mice exhibited reduced pericyte coverage and increased vascular leakage, suggesting a role for EC JAM-C in the development of functional tumor vessels. These findings provide evidence for a role for EC JAM-C in tumor growth and aggressiveness as well as recruitment of pericytes to newly formed blood vessels in a model of ovarian cancer.—Leinster, D. A., Colom, B., Whiteford, J. R., Ennis, D. P., Lockley, M., McNeish, I. A., Aurrand-Lions, M., Chavakis, T., Imhof, B. A., Balkwill, F. R., Nourshargh, S. Endothelial cell junctional adhesion molecule C plays a key role in the development of tumors in a murine model of ovarian cancer.
doi:10.1096/fj.13-230441
PMCID: PMC3819510  PMID: 23825230
pericytes; angiogenesis; vascular development; immune cell infiltrate
2.  Schwann cell-specific JAM-C-deficient mice reveal novel expression and functions for JAM-C in peripheral nerves 
The FASEB Journal  2012;26(3):1064-1076.
Junctional adhesion molecule-C (JAM-C) is an adhesion molecule expressed at junctions between adjacent endothelial and epithelial cells and implicated in multiple inflammatory and vascular responses. In addition, we recently reported on the expression of JAM-C in Schwann cells (SCs) and its importance for the integrity and function of peripheral nerves. To investigate the role of JAM-C in neuronal functions further, mice with a specific deletion of JAM-C in SCs (JAM-C SC KO) were generated. Compared to wild-type (WT) controls, JAM-C SC KO mice showed electrophysiological defects, muscular weakness, and hypersensitivity to mechanical stimuli. In addressing the underlying cause of these defects, nerves from JAM-C SC KO mice were found to have morphological defects in the paranodal region, exhibiting increased nodal length as compared to WTs. The study also reports on previously undetected expressions of JAM-C, namely on perineural cells, and in line with nociception defects of the JAM-C SC KO animals, on finely myelinated sensory nerve fibers. Collectively, the generation and characterization of JAM-C SC KO mice has provided unequivocal evidence for the involvement of SC JAM-C in the fine organization of peripheral nerves and in modulating multiple neuronal responses.—Colom, B., Poitelon, Y., Huang, W., Woodfin, A., Averill, S., Del Carro, U., Zambroni, D., Brain, S. D., Perretti, M., Ahluwalia, A., Priestley, J. V., Chavakis, T., Imhof, B. A., Feltri, M. L., Nourshargh, S. Schwann cell-specific JAM-C-deficient mice reveal novel expression and functions for JAM-C in peripheral nerves.
doi:10.1096/fj.11-196220
PMCID: PMC3370675  PMID: 22090315
adhesion molecules; tight junctions; peripheral nerves
3.  The spatiotemporal localization of JAM-C following sciatic nerve crush in adult rats 
Brain and Behavior  2012;2(4):402-414.
JAM-C is a junctional adhesion molecule, enriched at tight junctions on endothelial and epithelial cells, and also localized to Schwann cells at junctions between adjoining myelin end loops. The role of JAM-C following peripheral nerve injury (PNI) is currently unknown. We examined the localization of JAM-C after sciatic nerve crush injury in adult rats. JAM-C immunoreactivity was present in paranodes and incisures in sham surgery control nerve, but distal to the crush injury significantly decreased at three and 14 days. JAM-C was re-expressed at 28 days and, by 56 days, was significantly increased in the distal nerve compared to controls. In a 7-mm length of sciatic nerve sampled distal to the crush site, the densities of JAM-C immunoreactive paranodes increased in the distal direction. Conversely, the densities of JAM-C immunoreactive incisures were highest immediately distal to the crush site and decreased in the more distal direction. Further analysis revealed a strong correlation between JAM-C localization and remyelination. Fifty-six days after crush injury, greater densities of JAM-C paranodes were seen compared to the nodal marker jacalin, suggesting that paranodal JAM-C precedes node formation. Our data are the first to demonstrate a potential role of JAM-C in remyelination after PNI.
doi:10.1002/brb3.63
PMCID: PMC3432963  PMID: 22950044
JAM-C; paranodes; peripheral nerve injury; remyelination; Schwann cells
4.  Junctional adhesion molecule-C (JAM-C) regulates polarized neutrophil transendothelial cell migration in vivo 
Nature immunology  2011;12(8):761-769.
Neutrophil migration into inflamed tissues is a fundamental component of innate immunity. A decisive step in this process is the polarised migration of blood neutrophils through endothelial cells (ECs) lining the venular lumen (transendothelial cell migration; TEM) in a luminal to abluminal direction. Using real-time confocal imaging we report that neutrophils can exhibit disrupted polarised TEM (“hesitant” and “reverse”) in vivo. These events were noted in inflammation following ischemia-reperfusion injury, characterised by reduced expression of junctional adhesion molecule C (JAM-C) from EC junctions, and were enhanced by EC JAM-C blockade or genetic deletion. The results identify JAM-C as a key regulator of polarised neutrophil TEM in vivo and suggest that reverse TEM neutrophils can contribute to dissemination of systemic inflammation.
doi:10.1038/ni.2062
PMCID: PMC3145149  PMID: 21706006
5.  Junctional adhesion molecule (JAM)-C mediates leukocyte infiltration in response to ischemia reperfusion injury 
Objective
JAM-C is an adhesion molecule that has multiple roles in inflammation and vascular biology but many aspects of its functions under pathological conditions are unknown. Here we investigated the role of JAM-C in leukocyte migration in response to ischemia reperfusion (I/R) injury.
Methods and Results
Pre-treatment of mice with soluble JAM-C (sJAM-C), used as a pharmacological blocker of JAM-C-mediated reactions, significantly suppressed leukocyte migration in models of kidney and cremaster muscle I/R injury (39 and 51% inhibition, respectively). Furthermore, in the cremaster muscle model (studied by intravital microscopy), both leukocyte adhesion and transmigration were suppressed in JAM-C deficient mice (JAM-C−/−) and enhanced in mice over-expressing JAM-C in their endothelial cells (ECs). Analysis of JAM-C subcellular expression by immunoelectron microscopy indicated that in I/R-injured tissues, EC JAM-C was redistributed from cytoplasmic vesicles and EC junctional sites to non-junctional plasma membranes, a response that may account for the role of JAM-C in both leukocyte adhesion and transmigration under conditions of I/R injury.
Conclusions
The findings demonstrate a role for EC JAM-C in mediating leukocyte adhesion and transmigration in response to I/R injury and indicate the existence of a novel regulatory mechanism for redistribution and hence function of EC JAM-C in vivo.
doi:10.1161/ATVBAHA.109.187559
PMCID: PMC2746810  PMID: 19574560
JAM-C; Ischemia reperfusion injury; Leukocyte transmigration; Inflammation; Adhesion molecules

Results 1-5 (5)