Capacity of adipose tissue to promote growth and metastasis of a murine mammary carcinoma: effect of estrogen and progesterone.
Previously we have shown that a murine mammary carcinoma cell line, designated SPI, grows and metastasizes more efficiently in the mammary gland than in the subcutis. In this report, we examine the tissue specificity of this phenomenon. Our results show that SPI cells grow best in the mesenteric and ovarian fat pads and well in the mammary gland, but very poorly in the subcutis or peritoneal cavity. Massive dissemination of tumors from the ovarian and mesenteric sites occurs to the liver, spleen and diaphragm. In contrast, metastases from the mammary site occur primarily in the lung. Co-transplantation of a threshold number of SPI cells with mammary or ovarian fat fragments into the subcutis results in increased tumor growth, whereas very few tumors form in sham controls receiving no fat fragments. Removal of the ovaries of donor and recipient mice abrogates tumor growth in adipose tissue transplants. Estrogen can stimulate growth of SPI in adipose tissue sites, whereas progesterone inhibits growth. In contrast, in vivo growth of a stable metastatic variant selected from SPI cells was not inhibited by progesterone. SPI cells growing in ovarian and mesenteric fat pads showed increased expression of estrogen receptors and progesterone receptors, as well as detectable levels of epidermal-growth-factor receptors, whereas receptor levels decreased to baseline on tumors in the subcutis. The levels of estrogen-receptor mRNA reflect the corresponding functional expression of receptors; this finding suggests that the regulation of estrogen-receptor expression in this system is, at least in part, at the mRNA level. Our results are consistent with the model that adipose tissue exerts an estrogen-dependent positive regulatory effect on primary SPI tumor growth, and promotes the formation of metastases.
Elliott
B E
BE
Cancer Research Laboratories, Queen's University, Kingston, Ontario, Canada.
Tam
S P
SP
Dexter
D
D
Chen
Z Q
ZQ
D000273:Adipose Tissue; D000818:Animals; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000737:chemistry / Q000473:pathology* / Q000556:secondary; D066246:ErbB Receptors / Q000032:analysis; D004967:Estrogens / Q000502:physiology*; D005260:Female; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000737:chemistry / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009376:Neoplasms, Hormone-Dependent / Q000737:chemistry / Q000473:pathology*; D010052:Ovariectomy; D011374:Progesterone / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis / Q000235:genetics; D011980:Receptors, Progesterone / Q000032:analysis
D004967:Estrogens; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011374:Progesterone; D066246:ErbB Receptors