EFFECT OF ANTIPLATELET ANTIBODY ON THE DEVELOPMENT OF PULMONARY METASTASES FOLLOWING INJECTION OF CT26 COLON ADENOCARCINOMA, LEWIS LUNG-CARCINOMA, AND B-16 AMELANOTIC MELANOMA TUMOR-CELLS IN MICE

Abstract

Three different murine tumors, CT26 colon adenocarcinoma, Lewis lung carcinoma and B16 amelanotic melanoma, were injected into syngeneic mice (BALB/c and C57BL/6J) to test the effect of rabbit anti-mouse platelet antibody on the development of pulmonary metastases. Antiplatelet antibody, when injected i.p., decreased the platelet count from 1.5 .times. 106/.mu.l to 0.12 .times. 106/.mu.l at 6 h, which remained at this level for 24 h. Antiplatelet antibody given 6 h pre- and 18 h post-i.v. injection of tumor cells decreased the mean number of CT26 tumor nodules per lung by 57% (range, 47-65%) and decreased the mean nodule volume of tumor per lung by 37% (range, 0-71%) (124 experimental animals), when compared to the effect of nonimmune serum or irrelevant anti-immunoglobulin antibody in 136 control animals. With Lewis lung carcinoma, antiplatelet antibody decreased the mean number of tumor nodules by 62% (range, 57-78%) and decreased the mean nodule volume of tumors by 64% (range, 60-77%) using 48 experimental animals and 65 control animals. When tumor cells were given s.c., antiplatelet antibody given 6 h pre-injection, 18 h post-injection and every 48 h thereafter also decreased the mean number of metastases by 42% in 14 experimental and 15 control animals. With B16 amelanotic melanoma, antiplatelet antibody given 6 h pre- and 18 h post-injection decreased the mean number of tumor nodules by 85% and decreased the mean nodule volume of tumors by 66% using 9 experimental and 9 control animals. Similar results were obtained when all 3 tumors were injected 6 h after the injection of antiplatelet antibody. Negative results were obtained if antiplatelet antibody was injected 6 h after the injection of tumor cells. Since antiplatelet antibody has its maximum effect at 6 h, it is likely that platelets play their role in the development of pulmonary metastases during the 1st 12 h of tumor inoculation.