Generation of a monoclonal antibody that inhibits the procoagulant activity of various cancer cell lines.
BACKGROUND
Tumor procoagulant is one of the factors responsible for disseminated intravascular coagulation and metastasis. The authors found procoagulant activity in LK52 human squamous cell carcinoma cells, which they designated cancer cell-derived blood coagulating activity 1 (CCA-1). A monoclonal antibody (MoAb) was generated to characterize this CCA-1 procoagulant activity. To date, antibodies that show an inhibitory effect on procoagulant activity as well as high reactivity in cancer cells are well known for their tissue factor specificity.


METHODS
Characterization of the procoagulant activity of CCA-1 was performed and an anti-CCA-1 MoAb, FS01, was generated. CCA-1 expression on the cancer cell surface was examined by flow cytometry. Procoagulant activity of various cancer cell lines and the inhibitory effect of the FS01 MoAb on this procoagulant activity was monitored by a clot timer.


RESULTS
The enzymologic character differed from that of cancer procoagulant (CP). The FS01 MoAb inhibited the procoagulant activity of CCA-1, but did not inhibit that of tissue factor. A positive correlation was observed between the expression intensity of CCA-1 and the inhibitory effect of the FS01 MoAb on the procoagulant activity of cancer cell lines. Expression of CCA-1 was observed more frequently than that of tissue factor in human cancer cell lines.


CONCLUSIONS
The FS01 MoAb generated in the current study is a new antibody that reacts with various cancer cell lines, but not with normal cells. FS01 inhibits cancer cell-derived procoagulant activity and does not react with tissue factor and CP. CCA-1, which is recognized by the FS01 MoAb, appears to play a major role in cancer cell-derived procoagulant activity.
Inufusa
H
H
The First Department of Surgery, Kinki University School of Medicine, Osaka, Japan.
Adachi
T
T
Suzuki
M
M
Ando
O
O
Ohta
T
T
Kurimoto
M
M
Nakatani
Y
Y
Nakamura
M
M
Yasutomi
M
M
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000494:pharmacology*; D019774:Blood Coagulation Factor Inhibitors / Q000494:pharmacology; D001779:Blood Coagulation Factors / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D001780:Blood Coagulation Tests; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000556:secondary; D003546:Cysteine Endopeptidases / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D009500:Neutralization Tests; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000201:enzymology*
D000911:Antibodies, Monoclonal; D019774:Blood Coagulation Factor Inhibitors; D001779:Blood Coagulation Factors; D009363:Neoplasm Proteins; D003546:Cysteine Endopeptidases; C030910:cancer procoagulant