Effect of antiplatelet antibody on the development of pulmonary metastases following injection of CT26 colon adenocarcinoma, Lewis lung carcinoma, and B16 amelanotic melanoma tumor cells into 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 x 10(6)/microliters to 0.12 x 10(6)/microliters at 6 hr, which remained at this level for 24 hr. Antiplatelet antibody given 6 hr pre- and 18 hr post-i.v. injection of tumor cells decreased the mean number of CT26 tumor nodules per lung by 57% (range, 47 to 65%) and decreased the mean nodule volume of tumor per lung by 37% (range, 0 to 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 to 78%) and decreased the mean nodule volume of tumors by 64% (range, 60 to 77%) using 48 experimental animals and 65 control animals. When tumor cells were given s.c., antiplatelet antibody given 6 hr pre-injection, 18 hr post-injection, and every 48 hr 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 hr pre- and 18 hr 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 three tumors were injected 6 hr after the injection of antiplatelet antibody. However, negative results were obtained if antiplatelet antibody was injected 6 hr after the injection of tumor cells. Since antiplatelet antibody has its maximum effect at 6 hr, it is likely that platelets play their role in the development of pulmonary metastases during the first 12 hr of tumor inoculation.