title: Endothelial cell junctional adhesion molecule C plays a key role in the development of tumors in a murine model of ovarian cancer.
abstract: 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.
authors.affiliation: 2Centre for Microvascular Research, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M6BQ, UK. s.nourshargh@qmul.ac.uk.
authors.forename: David A
authors.initials: DA
authors.lastname: Leinster
authors.forename: Bartomeu
authors.initials: B
authors.lastname: Colom
authors.forename: James R
authors.initials: JR
authors.lastname: Whiteford
authors.forename: Darren P
authors.initials: DP
authors.lastname: Ennis
authors.forename: Michelle
authors.initials: M
authors.lastname: Lockley
authors.forename: Iain A
authors.initials: IA
authors.lastname: McNeish
authors.forename: Michel
authors.initials: M
authors.lastname: Aurrand-Lions
authors.forename: Triantafyllos
authors.initials: T
authors.lastname: Chavakis
authors.forename: Beat A
authors.initials: BA
authors.lastname: Imhof
authors.forename: Frances R
authors.initials: FR
authors.lastname: Balkwill
authors.forename: Sussan
authors.initials: S
authors.lastname: Nourshargh
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C448000:JAM3 protein, human; C486723:Jam3 protein, mouse
keywords: angiogenesis; immune cell infiltrate; pericytes; vascular development