Ley glycolipid-recognizing monoclonal antibody inhibits procoagulant activity and metastasis of human adenocarcinoma.
Tumor procoagulant is associated with cancer at advanced stages of malignancy such as infiltration and metastasis. In the present study, we investigated the role of Ley glycolipid in the mechanism of cancer metastasis. Ley glycolipid acts as an important cofactor in the expression of the blood-coagulating activity of cancer cell-derived coagulating activity 1 (CCA-1), which is one of the known tumor procoagulants. Monoclonal antibody (MoAb) FS01, which serves as the Ley-recognizing epitope, inhibits the procoagulant activity of CCA-1 was found to dose-dependently inhibit the procoagulant activity of normal plasma induced by the human lung adenocarcinoma cell line, HAL8, which shows a high level of Ley expression. It did not, however, inhibit the procoagulant activity of the human colon cancer cell line, RPMI4788, which does not express Ley. Administration of FS01 MoAb inhibited lung metastasis of HAL8 cells, but not that of RPMI4788. The absence of antibody-dependent cellular cytotoxicity and complement-mediated cytotoxicity of FS01 MoAb against the HAL8 cell line suggests that the inhibition of HAL8 metastasis by FS01 MoAb derives from the inhibition of blood-coagulating activity of the latter. These findings indicate that Ley glycolipid plays an important role in the mechanism of cancer metastasis via the procoagulant activity of CCA-1.
Inufusa
H
H
The First Department of Surgery, Kinki University School of Medicine, Osaka 589-8511, Japan. inufsa@surg1.med.kindai.ac.jp
Adachi
T
T
Kiyokawa
T
T
Nakatani
Y
Y
Wakano
T
T
Nakamura
M
M
Okuno
K
K
Shiozaki
H
H
Yamamoto
S
S
Suzuki
M
M
Ando
O
O
Kurimoto
M
M
Miyake
M
M
Yasutomi
M
M
D000230:Adenocarcinoma / Q000276:immunology / Q000517:prevention & control* / Q000556:secondary; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001779:Blood Coagulation Factors / Q000378:metabolism*; D001780:Blood Coagulation Tests; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D003546:Cysteine Endopeptidases / Q000187:drug effects* / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006017:Glycolipids / Q000276:immunology*; D007983:Lewis Blood Group Antigens / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D001779:Blood Coagulation Factors; D006017:Glycolipids; D007983:Lewis Blood Group Antigens; C094162:Lewis Y antigen; D009363:Neoplasm Proteins; D003546:Cysteine Endopeptidases; C030910:cancer procoagulant