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

Wang C, Gao C, Meng K, Qiao H, Wang Y - PLoS ONE (2015)

Bottom Line: In addition, MMP-2 was remarkably up-regulated, whereas E-cadherin was down-regulated in these MCF-7 cells.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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China.

ABSTRACT

Background and aims: 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.

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Related in: MedlinePlus

Immunohistochemical staining of IGFBP-2 in human adipocytes and MMP-2 in human breast tumors.4A. Sections of metastatic and non-metastatic breast tumors and surrounding adipocytes were stained by hematoxylin and eosin (magnification 100 ×). Peritumoral adipocytes from infiltrant metastatic mammary tumors appear smaller and more spindle-shaped. 4B. Representative microphotographs show IGFBP-2 in human adipocytes around metastatic and non-metastatic breast tumors. Human adipocytes around metastatic breast tumors had higher levels of IGFBP-2 than did those around non-metastatic primary tumors. Arrowheads indicate IGFBP-2 positive cells (magnification 100 ×). 4C. Representative microphotographs show MMP-2 in metastatic and non-metastatic human breast tumors. Metastatic human breast tumors had higher levels of MMP-2 than did non-metastatic tumor tissue. Ellipse indicates MMP-2 positive cells at the edge of tumor (magnification 100 ×). The negative control was obtained by omitting the primary antibody.
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pone.0119348.g004: Immunohistochemical staining of IGFBP-2 in human adipocytes and MMP-2 in human breast tumors.4A. Sections of metastatic and non-metastatic breast tumors and surrounding adipocytes were stained by hematoxylin and eosin (magnification 100 ×). Peritumoral adipocytes from infiltrant metastatic mammary tumors appear smaller and more spindle-shaped. 4B. Representative microphotographs show IGFBP-2 in human adipocytes around metastatic and non-metastatic breast tumors. Human adipocytes around metastatic breast tumors had higher levels of IGFBP-2 than did those around non-metastatic primary tumors. Arrowheads indicate IGFBP-2 positive cells (magnification 100 ×). 4C. Representative microphotographs show MMP-2 in metastatic and non-metastatic human breast tumors. Metastatic human breast tumors had higher levels of MMP-2 than did non-metastatic tumor tissue. Ellipse indicates MMP-2 positive cells at the edge of tumor (magnification 100 ×). The negative control was obtained by omitting the primary antibody.

Mentions: We chose 10 metastatic pathologic samples and 10 non-metastatic pathologic samples to be stained by hematoxylin and eosin. We found that the adipocytes around metastatic tumors showed dramatic morphological changes compared with those surrounding non-metastatic tumors. They looked smaller and more spindle-shaped, especially when the tumor cells had broken through the basement membrane. We next aimed to determine the cellular origin and distribution of IGFBP-2 in metastatic and non-metastatic mammary tumor samples. We analyzed by immunohistochemistry the presence of MMP-2 in tumor cells and IGFBP-2 in the adipocytes around tumor cells in samples of human ductal infiltrant mammary tumors. As Fig. 4B shows, human adipocytes around metastatic breast tumors had higher levels of IGFBP-2 than did those around non-metastatic primary breast tumors.


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

Wang C, Gao C, Meng K, Qiao H, Wang Y - PLoS ONE (2015)

Immunohistochemical staining of IGFBP-2 in human adipocytes and MMP-2 in human breast tumors.4A. Sections of metastatic and non-metastatic breast tumors and surrounding adipocytes were stained by hematoxylin and eosin (magnification 100 ×). Peritumoral adipocytes from infiltrant metastatic mammary tumors appear smaller and more spindle-shaped. 4B. Representative microphotographs show IGFBP-2 in human adipocytes around metastatic and non-metastatic breast tumors. Human adipocytes around metastatic breast tumors had higher levels of IGFBP-2 than did those around non-metastatic primary tumors. Arrowheads indicate IGFBP-2 positive cells (magnification 100 ×). 4C. Representative microphotographs show MMP-2 in metastatic and non-metastatic human breast tumors. Metastatic human breast tumors had higher levels of MMP-2 than did non-metastatic tumor tissue. Ellipse indicates MMP-2 positive cells at the edge of tumor (magnification 100 ×). The negative control was obtained by omitting the primary antibody.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4352027&req=5

pone.0119348.g004: Immunohistochemical staining of IGFBP-2 in human adipocytes and MMP-2 in human breast tumors.4A. Sections of metastatic and non-metastatic breast tumors and surrounding adipocytes were stained by hematoxylin and eosin (magnification 100 ×). Peritumoral adipocytes from infiltrant metastatic mammary tumors appear smaller and more spindle-shaped. 4B. Representative microphotographs show IGFBP-2 in human adipocytes around metastatic and non-metastatic breast tumors. Human adipocytes around metastatic breast tumors had higher levels of IGFBP-2 than did those around non-metastatic primary tumors. Arrowheads indicate IGFBP-2 positive cells (magnification 100 ×). 4C. Representative microphotographs show MMP-2 in metastatic and non-metastatic human breast tumors. Metastatic human breast tumors had higher levels of MMP-2 than did non-metastatic tumor tissue. Ellipse indicates MMP-2 positive cells at the edge of tumor (magnification 100 ×). The negative control was obtained by omitting the primary antibody.
Mentions: We chose 10 metastatic pathologic samples and 10 non-metastatic pathologic samples to be stained by hematoxylin and eosin. We found that the adipocytes around metastatic tumors showed dramatic morphological changes compared with those surrounding non-metastatic tumors. They looked smaller and more spindle-shaped, especially when the tumor cells had broken through the basement membrane. We next aimed to determine the cellular origin and distribution of IGFBP-2 in metastatic and non-metastatic mammary tumor samples. We analyzed by immunohistochemistry the presence of MMP-2 in tumor cells and IGFBP-2 in the adipocytes around tumor cells in samples of human ductal infiltrant mammary tumors. As Fig. 4B shows, human adipocytes around metastatic breast tumors had higher levels of IGFBP-2 than did those around non-metastatic primary breast tumors.

Bottom Line: In addition, MMP-2 was remarkably up-regulated, whereas E-cadherin was down-regulated in these MCF-7 cells.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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China.

ABSTRACT

Background and aims: 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.

Show MeSH
Related in: MedlinePlus