CAPACITY OF ADIPOSE-TISSUE TO PROMOTE GROWTH AND METASTASIS OF A MURINE MAMMARY-CARCINOMA - EFFECT OF ESTROGEN AND PROGESTERONE
CAPACITY OF ADIPOSE-TISSUE TO PROMOTE GROWTH AND METASTASIS OF A MURINE MAMMARY-CARCINOMA - EFFECT OF ESTROGEN AND PROGESTERONE
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DOI：
10.1002/ijc.2910510314
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发表时间：
1992-05-28
影响因子：
6.4
通讯作者：
CHEN, ZQ
中科院分区：
文献类型：
--
作者：
ELLIOTT, BE;TAM, SP;CHEN, ZQ
以前，我们已经表明，小鼠乳腺癌细胞系，指定SPI，生长和转移更有效地在乳腺比皮下组织。在这份报告中，我们研究了这种现象的组织特异性。我们的结果表明，SPI细胞在肠系膜和卵巢脂肪垫中生长最好，在乳腺中生长良好，但在皮下组织或腹膜腔中生长非常差。肿瘤从卵巢和肠系膜部位大量播散至肝、脾和膈。相反，来自乳腺部位的转移主要发生在肺中。将阈值数量的SPI细胞与乳腺或卵巢脂肪碎片共移植到皮下组织中导致肿瘤生长增加，而在不接受脂肪碎片的假手术对照中很少形成肿瘤。切除供体和受体小鼠的卵巢可抑制脂肪组织移植物中的肿瘤生长。雌激素可刺激脂肪组织部位SPI的生长，而孕酮则抑制生长。与此相反，在体内生长的一个稳定的转移性的变种，从SPI细胞选择不抑制孕酮。在卵巢和肠系膜脂肪垫中生长的SPI细胞显示雌激素受体和孕激素受体的表达增加，以及表皮生长因子受体的可检测水平，而皮下组织中肿瘤的受体水平下降至基线。雌激素受体mRNA的水平反映了相应的受体功能表达;这一发现表明，该系统中雌激素受体表达的调节至少部分是在mRNA水平。我们的研究结果与脂肪组织对原发性SPI肿瘤生长发挥雌激素依赖性正调控作用并促进转移瘤形成的模型一致。
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.