Interaction of endosialin/TEM1 with extracellular matrix proteins mediates cell adhesion and migration.
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.
Tomkowicz
Brian
B
Morphotek, Inc., 210 Welsh Pool Road, Exton, PA 19341, USA.
Rybinski
Katherine
K
Foley
Brian
B
Ebel
Wolfgang
W
Kline
Brad
B
Routhier
Eric
E
Sass
Philip
P
Nicolaides
Nicholas C
NC
Grasso
Luigi
L
Zhou
Yuhong
Y
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
D015703:Antigens, CD; D000951:Antigens, Neoplasm; C078203:CD248 protein, human; D016326:Extracellular Matrix Proteins