HIGHLY METASTATIC 13762NF RAT MAMMARY ADENOCARCINOMA CELL CLONES STIMULATE BONE-MARROW BY SECRETION OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR INTERLEUKIN-3 ACTIVITY

Circulating neutrophil (polymorphonuclear leukocyte levels rise 50-fol d in 13762NF tumor-bearing rats in proportion to the tumor's metastati c potential. Purified tumor-elicited neutrophils enhance metastasis of syngeneic tumor cells when co-injected intravenously; however, circul ating and phorbol ester-activated polymorphonuclear neutrophils do not . The purpose of this study was to elucidate the source of tumor-elici ted neutrophils in metastatic tumor-bearing rats. We examined the bone marrow in rats bearing tumors of poorly, moderately, and highly metas tatic cell clones. Marrow from rats with highly metastatic tumors had increased cellularity (100%), myeloid to erythroid ratio (10:1), and m egakaryocytes compared with control rats (cellularity, similar to 80%; myeloid to erythroid ratio, 5:1), with marrows from rats with moderat ely metastatic tumors having intermediate values. This suggested produ ction of a colony-stimulating factor by the metastatic cells. To confi rm this, bone marrow colony formation from control and tumor-bearing r ats was compared. Colony number increased in proportion to the metasta tic potential of the tumor. Conditioned medium from metastatic cells s upported growth of the granulocyte-macrophage colony-stimulating facto r/interleukin-3-dependent 32Dc13 cell line, but media from nonmetastat ic or moderately metastatic cells did not. Antibodies to murine granul ocyte-macrophage colony-stimulating factor neutralized 32Dc13 growth i n tumor cell conditioned medium. These results suggest production of a granulocyte-macrophage colony-stimulating factor or interleukin-3-lik e activity by highly metastatic 13762NF clones and implicate a possibl e role for colony-stimulating factors in regulating the metastatic pot ential of mammary adenocarcinoma cell clones.