Suppression of experimental lung colonization of a metastatic variant of murine colon adenocarcinoma 26 by a monoclonal antibody 8F11 inhibiting tumor cell-induced platelet aggregation.
We have previously established and characterized two monoclonal antibodies, 8F11 and 20A11, that recognize an Mr 44,000 membrane glycoprotein of metastatic murine colon 26 cells. Both monoclonal antibodies inhibit platelet aggregation induced by the tumor cells in vitro. In this report, the inhibitory effect of 8F11 on lung colonization of i.v.-inoculated tumor cells was examined. The i.v. administration of 8F11 suppressed lung colonization of NL-17, a highly metastatic variant of colon 26. Inhibition of NL-17 lung colonization by 8F11 was dose dependent with a maximum of 80% inhibition at a dose of 800 micrograms 8F11/mouse. 8F11 did not inhibit metastases at doses lower than 100 micrograms/mouse. Inhibition of pulmonary metastases by 8F11 was greatest when the antibody was administered 2 h before tumor inoculation. The effect was diminished when the antibody was given 2 h after tumor inoculation. The pulmonary retention of i.v.-inoculated radiolabeled NL-17 cells was decreased by 8F11. F(ab')2 fragments of 8F11 also effectively inhibited lung colonization by NL-17 cells, suggesting that mechanisms unrelated to immune-mediated destruction are involved. These results indicate that the monoclonal antibody 8F11 suppresses the lung colonization of NL-17 cells by interfering with the initial arrest of tumor cells in the lung vasculature through the inhibition of tumor cell-platelet interaction.
Sugimoto
Y
Y
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
Watanabe
M
M
Oh-hara
T
T
Sato
S
S
Isoe
T
T
Tsuruo
T
T
D000230:Adenocarcinoma / Q000517:prevention & control* / Q000556:secondary*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000473:pathology*; D005260:Female; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000473:pathology
D000911:Antibodies, Monoclonal; D010975:Platelet Aggregation Inhibitors