Mature adipocytes, but not preadipocytes, promote the growth of breast carcinoma cells in collagen gel matrix culture through cancer-stromal cell interactions
Mature adipocytes, but not preadipocytes, promote the growth of breast carcinoma cells in collagen gel matrix culture through cancer-stromal cell interactions
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DOI：
10.1002/path.1430
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发表时间：
2003-10-01
影响因子：
7.3
通讯作者：
Sugihara, H
中科院分区：
文献类型：
--
作者：
Manabe, Y;Toda, S;Sugihara, H
肿瘤和间质细胞之间的相互作用对肿瘤细胞的生长和侵袭至关重要。最近有研究表明，成熟脂肪细胞是一种特殊类型的基质细胞，在乳房中大量存在，它会影响某些上皮细胞类型的生物学行为。然而，成熟脂肪细胞和乳腺癌细胞之间相互作用的性质仍然不清楚。本研究以成熟的大鼠脂肪细胞作为脂肪组织的主要细胞类型，通过对乳腺癌细胞系[人雌激素受体阳性细胞系MCF-7、ZR75-1和T47-D以及雌激素受体阴性小鼠细胞系MMT-060562]的摄取、细胞凋亡指数和E-钙粘附素的免疫组织化学表达的分析，探讨了成熟的大鼠脂肪细胞对乳腺癌细胞系[人雌激素受体阳性细胞系MCF-7、ZR75-1和T47-D以及雌激素受体阴性小鼠细胞系MMT 060562]生长、凋亡和细胞黏附的影响。作为参考，研究了大鼠前脂肪细胞(未成熟脂肪细胞)对细胞系行为的影响。细胞系在含有成熟脂肪细胞或前脂肪细胞的三维胶原凝胶基质中培养。成熟脂肪细胞显著促进除MMT-060562细胞外的所有细胞对BrdU的摄取。前脂肪细胞使T47-D细胞摄取减少，而对MCF-7、ZR75-1和MMT 060562细胞的摄取无影响。成熟脂肪细胞或前脂肪细胞不影响任何细胞系的凋亡指数。成熟脂肪细胞对E-钙粘蛋白的表达无明显影响，但前脂肪细胞可明显促进MCF-7和T47-D细胞的E-钙粘蛋白表达，而对R75-1和MMT 060562细胞无明显影响。这些数据表明，成熟脂肪细胞可能通过对ER阳性肿瘤细胞的生长促进作用参与调控乳腺癌肿瘤生长的机制。版权所有(C)2003 John Wiley Sons，Ltd.
Interaction between cancer and stromal cells is critical for tumour cell growth and invasion. It has recently been suggested that mature adipocytes, a specific type of stromal cell that is abundant in the breast, affect the biological behaviour of some epithelial cell types. However, the nature of the interaction between mature adipocytes and breast cancer cells remains unclear. The present study has examined the effects of mature rat adipocytes, as the main cell type in adipose tissue, on the growth, apoptosis, and cell adhesion of breast carcinoma cell lines [human oestrogen receptor (ER)-positive cell lines MCF-7, ZR75-1, and T47-D; and the ER-negative mouse cell line MMT 060562] by analysing bromodeoxyuridine (BrdU) uptake, apoptotic indices, and immunohistochemical expression of E-cadherin. As a reference, the effects of rat preadipocytes (immature adipocytes) on the behaviour of the cell lines were examined. The cell lines were cultured in a three-dimensional collagen gel matrix with mature adipocytes or preadipocytes. Mature adipocytes significantly promoted BrdU uptake by all cell lines other than MMT 060562 cells. Preadipocytes decreased the uptake of T47-D cells and had no effect on that of MCF-7, ZR75-1 or MMT 060562 cells. Mature adipocytes or preadipocytes did not affect the apoptotic indices of any of the cell lines. Mature adipocytes did not influence E-cadherin expression in any of the cell lines, but preadipocytes clearly promoted E-cadherin expression by MCF-7 and T47-D cells, but not by R75-1 and MMT 060562 cells. These data suggest that mature adipocytes may be involved in the mechanisms regulating the growth of breast cancer mass through their growth-promoting effect on ER-positive tumour cells. Copyright (C) 2003 John Wiley Sons, Ltd.