title: Interaction of endosialin/TEM1 with extracellular matrix proteins mediates cell adhesion and migration.
abstract: Endosialin/TEM1 was originally discovered as a human embryonic fibroblast-specific antigen and was later found to be differentially expressed in tumor stroma and endothelium. Endosialin/TEM1 overexpression has been observed in many cancers of various tissue origin, including colon, breast, pancreatic, and lung. The knockout (KO) mouse model showed the absence of endosialin/TEM1 expression reduced growth, invasion, and metastasis of human tumor xenografts. In addition, lack of endosialin/TEM1 led to an increase in small immature blood vessels and decreased numbers of medium and large tumor vessels. This abnormal angiogenic response could be responsible for the reduced tumor growth and invasion observed in endosialin/TEM1 KO mice, suggesting a role for endosialin/TEM1 in controlling the interaction among tumor cells, endothelia, and stromal matrix. Here we report the identification of fibronectin (FN) and collagen types I and IV as specific ligands for endosialin/TEM1. More importantly, cells expressing endosialin/TEM1 exhibit enhanced adhesion to FN as well as enhanced migration through matrigel, although these properties could be blocked by a humanized antibody directed against human endosialin/TEM1. Our results pinpoint to a molecular mechanism by which expression of endosialin/TEM1 in the tumor stroma and endothelium may support tumor progression and invasion.
authors.affiliation: Morphotek, Inc., 210 Welsh Pool Road, Exton, PA 19341, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Tomkowicz
authors.forename: Katherine
authors.initials: K
authors.lastname: Rybinski
authors.forename: Brian
authors.initials: B
authors.lastname: Foley
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Ebel
authors.forename: Brad
authors.initials: B
authors.lastname: Kline
authors.forename: Eric
authors.initials: E
authors.lastname: Routhier
authors.forename: Philip
authors.initials: P
authors.lastname: Sass
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Nicolaides
authors.forename: Luigi
authors.initials: L
authors.lastname: Grasso
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015153:Blotting, Western; D016466:CHO Cells; D002448:Cell Adhesion; D002465:Cell Movement; D006224:Cricetinae; D003412:Cricetulus; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D006868:Hydrolysis; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C078203:CD248 protein, human; D016326:Extracellular Matrix Proteins