Expression of the vascular endothelial cell protein C receptor in epithelial tumour cells.
The rat monoclonal antibody LMR-42 has previously been shown to react with an external epitope of a plasma membrane protein with a M(r) of approximately 55,000 that was upregulated in multidrug-resistant (MDR) tumour cells. Here, we report the isolation of the cDNA encoding the LMR-42 antigen from the MDR human fibrosarcoma cell line HT1080/DR4 and the lung cancer cell line GLC4/ADR by expression cloning. Sequence analysis showed that the LMR-42 antigen is identical to the endothelial cell protein C receptor (EPCR). Using the LMR-42 Mab for cytochemical analyses of a disease-oriented panel of 45 non-drug selected tumour cell lines of the National Cancer Institute (NCI), we found high EPCR expression in 47% of the primary tumour cell lines, including melanomas, renal- and colon carcinomas. In a small panel of human tumours, occasionally very high EPCR expression was detected in endothelial vessels, but expression in the tumour cells was a rare event. The functional significance of overexpression of EPCR on both primary and drug-selected tumour cells is still unclear. As the protein is related to MHC class I molecules and shares no characteristics with any of the currently known transporter proteins, EPCR is not expected to play a causal role in the resistant phenotype of the MDR tumour cells. Nevertheless, exposure of tumour cells to cytostatic drugs may frequently lead to EPCR overexpression. Since EPCR is known to play a pivotal role in preventing blood coagulation through binding of (activated) protein C, it might endow tumour cells, both of mesenchymal and epithelial derivations, with increased growth potential by local anti-coagulant activity.
Department of Pathology, Free University Medical Center, De Boelelaan 1117 1081 HV, Amsterdam, The Netherlands.
George L
GL
Scheffer
Marcel J
MJ
Flens
Sandra
S
Hageman
Miguel A
MA
Izquierdo
Robert H
RH
Shoemaker
Rik J
RJ
Scheper
D000911:Antibodies, Monoclonal / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D001779:Blood Coagulation Factors; D018076:DNA, Complementary / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D001779:Blood Coagulation Factors; D018076:DNA, Complementary; D011956:Receptors, Cell Surface; C091963:activated protein C receptor