Human adipocytes stimulate invasion of breast cancer MCF-7 cells by secreting IGFBP-2.
OBJECTIVE
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.


METHODS
To 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.


RESULTS
The 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.


CONCLUSIONS
IGFBP-2 secreted by mature adipocytes plays a key role in promoting the metastatic ability of MCF-7 breast cancer cells.
State Key Laboratory of Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China.
Chen
C
Wang
The Center for Clinical Reproductive Medicine, Jiangsu Province Hospital, Nanjing 210029, China.
Chao
C
Gao
The Gulou Hospital attached to Nanjing University, Nanjing 210008, China.
Kui
K
Meng
State Key Laboratory of Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China.
Haishi
H
Qiao
State Key Laboratory of Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China.
Yong
Y
Wang
D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism*; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis
C577903:IGFBP2 protein, human; D018971:Insulin-Like Growth Factor Binding Protein 2