Abstract
Background and AimsA better understanding of the effects of human adipocytes on breast cancer cells may lead to the development of new treatment strategies. We explored the effects of adipocytes on the migration and invasion of breast cancer cells both in vitro and in vivo.MethodsTo study the reciprocal effects of adipocytes and cancer cells, we co-cultured human mature adipocytes and breast cancer cells in a system devoid of heterogeneous cell-cell contact. To analyze the factors that were secreted from adipocytes and that affected the invasive abilities of breast cancer cells, we detected different cytokines in various co-culture media. To study the communication of mature adipocytes and breast cancer cells in vivo, we chose 10 metastatic pathologic samples and 10 non-metastatic pathologic samples to do immunostaining.ResultsThe co-culture media of human MCF-7 breast cancer cells and human mature adipocytes increased motility of MCF-7 cells. In addition, MMP-2 was remarkably up-regulated, whereas E-cadherin was down-regulated in these MCF-7 cells. Based on our co-culture medium chip results, we chose four candidate cytokines and tested their influence on metastasis individually. We found that IGFBP-2 enhanced the invasion ability of MCF-7 cells in vitro more prominently than did the other factors. In vivo, metastatic human breast tumors had higher levels of MMP-2 than did non-metastatic tumor tissue, whereas adipocytes around metastatic breast tumors had higher levels of IGFBP-2 than did adipocytes surrounding non-metastatic breast tumors.ConclusionsIGFBP-2 secreted by mature adipocytes plays a key role in promoting the metastatic ability of MCF-7 breast cancer cells.
Highlights
Adipocytes are the most abundant and perhaps the most active component of the breast cancer stroma [1,2]
We found that insulin-like growth factor binding protein-2 (IGFBP-2) enhanced the invasion ability of MCF-7 cells in vitro more prominently than did the other factors
We used MCF-7, which is a cancer cell line with low metastatic potential, for scratch assays and found that medium conditioned by co-cultures (CAA-conditioned medium (CM)) significantly accelerated the closure of the cell-cleared area compared to unconditioned control medium (C-CM) (Fig. 1A)
Summary
Adipocytes are the most abundant and perhaps the most active component of the breast cancer stroma [1,2]. When human breast cancer cells break through the basal membrane, they are exposed to adipocytes in the immediate tumor microenvironment as they traverse the underlying connective tissue towards the bloodstream. Recent accumulating evidence has reported that the tumor-adjacent adipose tissue is a key component of breast cancer progression. Determining which adipocyte-derived factors contribute to stimulating breast cancer cell progression still needs much more investigation. A better understanding of the effects of human adipocytes on breast cancer cells may lead to the development of new treatment strategies. We explored the effects of adipocytes on the migration and invasion of breast cancer cells both in vitro and in vivo
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