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-fold in 13762NF tumor-bearing rats in proportion to the tumor's metastatic potential. Purified tumor-elicited neutrophils enhance metastasis of syngeneic tumor cells when co-injected intravenously; however, circulating and phorbol ester-activated polymorphonuclear neutrophils do not. The purpose of this study was to elucidate the source of tumor-elicited neutrophils in metastatic tumor-bearing rats. We examined the bone marrow in rats bearing tumors of poorly, moderately, and highly metastatic cell clones. Marrow from rats with highly metastatic tumors had increased cellularity (100%), myeloid to erythroid ratio (10:1), and megakaryocytes compared with control rats (cellularity, approximately 80%; myeloid to erythroid ratio, 5:1), with marrows from rats with moderately metastatic tumors having intermediate values. This suggested production of a colony-stimulating factor by the metastatic cells. To confirm this, bone marrow colony formation from control and tumor-bearing rats was compared. Colony number increased in proportion to the metastatic potential of the tumor. Conditioned medium from metastatic cells supported growth of the granulocyte-macrophage colony-stimulating factor/interleukin-3-dependent 32Dcl3 cell line, but media from nonmetastatic or moderately metastatic cells did not. Antibodies to murine granulocyte-macrophage colony-stimulating factor neutralized 32Dcl3 growth in tumor cell conditioned medium. These results suggest production of a granulocyte-macrophage colony-stimulating factor or interleukin-3-like activity by highly metastatic 13762NF clones and implicate a possible role for colony-stimulating factors in regulating the metastatic potential of mammary adenocarcinoma cell clones.
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015152:Blotting, Northern; D001853:Bone Marrow / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D007377:Interleukin-3 / Q000096:biosynthesis* / Q000494:pharmacology; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D014407:Tumor Cells, Cultured
D007377:Interleukin-3; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor