Procoagulant activity in cancer cells is dependent on tissue factor expression.
Procoagulant activity of pairs of cell lines, which were derived from the same original cell type but which possess different growth characteristics and metastatic properties, was examined. The following characteristics were considered suggestive of a greater likelihood of metastatic potential: high histological grade; establishment of the line from a metastatic rather than a nonmetastatic cancer; increased tumorigenicity in nude mice; and/or estrogen receptor-negative mammary cancer. Procoagulant activity was evaluated by a two stage clotting assay. Procoagulant activity was highly variable, with up to a 1,300-fold difference, among the cancer cell lines examined. The rate of clot formation was factor VII dependent and was totally inhibited by an anti tissue factor monoclonal antibody, indicating that tissue factor was the only significant procoagulant present in these cancer cells. Tissue factor antigen expression, evaluated by ELISA, correlated with procoagulant activity. In all pairs of cancer cell lines, those with characteristics of increased proliferative potential had increased tissue factor levels compared to cell lines that originated from the same cell type, but which possess less aggressive characteristics. Tissue factor activity in these cancer cells was increased by cell lysis or by exposure of intact cells to a calcium ionophore, similar to results previously obtained in fibroblasts. Tissue factor mRNA was evaluated by northern blot analysis using a specific probe complementary to tissue factor mRNA. The previously described predominant tissue factor mRNA species of 2.2 kb was identified in the majority of cancer cell lines examined, but tissue factor mRNA species of 3.2 to 3.4 kb were also identified.(ABSTRACT TRUNCATED AT 250 WORDS)
Hu
T
T
Yale University School of Medicine, New Haven, CT 06510.
Bach
R R
RR
Horton
R
R
Konigsberg
W H
WH
Todd
M B
MB
D000230:Adenocarcinoma; D001777:Blood Coagulation; D015152:Blotting, Northern; D001943:Breast Neoplasms; D002292:Carcinoma, Renal Cell; D002295:Carcinoma, Transitional Cell; D002460:Cell Line; D005770:Gastrointestinal Neoplasms; D015870:Gene Expression; D006801:Humans; D007680:Kidney Neoplasms; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000032:analysis; D013925:Thromboplastin / Q000032:analysis / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D013925:Thromboplastin