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Molecular Connections between Cancer Cell Metabolism and the Tumor Microenvironment
Correction published on 22 September 2015, see Int. J. Mol. Sci. 2015, 16(9), 22957-22959.
Open AccessArticle

Exposure of Tumor-Associated Macrophages to Apoptotic MCF-7 Cells Promotes Breast Cancer Growth and Metastasis

Department of Pharmacology, Peking University, Health Science Center, Beijing 100191, China
Beijing N&N Genetech Company, Beijing 100082, China
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada
Authors to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Int. J. Mol. Sci. 2015, 16(6), 11966-11982;
Received: 25 April 2015 / Revised: 18 May 2015 / Accepted: 19 May 2015 / Published: 26 May 2015
(This article belongs to the Collection Advances in Molecular Oncology)
Tumor-associated macrophages (TAMs) have been found to be associated with the progression and metastasis of breast cancer. To clarify the mechanisms underlying the crosstalk between TAMs and cancer stem cells (CSCs) in breast cancer recurrence and metastasis, we used a co-culture model of macrophages and apoptotic human breast cancer cell line MCF-7 cells to investigate the effects of TAMs on MCF-7 in vitro and in vivo. Macrophages co-cultured with apoptotic MCF-7 had increased tumor growth and metastatic ability in a nude mouse transplantation assay. The macrophages exposed to apoptotic cells also induce an increase in the proportion of CD44+/CD24 cancer stem-like cells, as well as their proliferative ability accompanied with an increase in mucin1 (MUC1) expression. During this process, macrophages secreted increased amounts of interleukin 6 (IL-6) leading to increased phosphorylation of signal transducers and activators of transcription 3 (STAT3), which likely explains the increased transcription of STAT3 target genes such as TGF-β1 and HIF-1α. Our results indicate that when cancer cells endure chemotherapy induced apoptosis, macrophages in their microenvironment can then activate cancer stem cells to promote cancer growth and metastasis by secreting IL-6, which activates STAT3 phosphorylation to regulate the transcription of its downstream target genes. View Full-Text
Keywords: cancer stem cells; apoptosis; TAMs; metastasis; IL-6; STAT3 cancer stem cells; apoptosis; TAMs; metastasis; IL-6; STAT3
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Zhou, N.; Zhang, Y.; Zhang, X.; Lei, Z.; Hu, R.; Li, H.; Mao, Y.; Wang, X.; Irwin, D.M.; Niu, G.; Tan, H. Exposure of Tumor-Associated Macrophages to Apoptotic MCF-7 Cells Promotes Breast Cancer Growth and Metastasis. Int. J. Mol. Sci. 2015, 16, 11966-11982.

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