*Integrated Biomedical Science Graduate Program, Department of Pediatrics, School of Medicine & Public Health, The Ohio State University, Columbus, Ohio, USA; and â Center for Childhood Cancer, Childrenâs Research Institute, Columbus, Ohio, USA ABSTRACT Bone is the primary anatomical site of breast cancer metastasis, and bone metastasis is associated with increased morbidity and mortality. Mesenchymal stem cells (MSC) are a predominant ï¬broblast cell population within the bone marrow, and metastatic breast cancer cells that seed within bone would predictably encounter MSC or their soluble factors. Therefore, we examined the impact of primary human MSC on a panel of estrogen receptor-alpha (ER )-positive (MCF-7, T47D, BT474, and ZR-75â1) and ER -negative (MDA-MB-231 and MDA-MB-468) human breast tumor cell lines. All ER -positive breast tumor cell lines displayed low basal activation of signal transducer and activator of transcription 3 (STAT3) until exposed to MSC, which induced chronic phosphorylation of STAT3 on tyrosine-705. Paracrine IL-6 was found to be the principal mediator of STAT3 phosphorylation in coculture studies, and MSC induction of STAT3 phosphorylation was lost when IL-6 was depleted from MSC conditioned media or the IL-6 receptor was blocked on tumor cells. Enhanced tumor cell growth rates were observed in
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Interleukin-6 is a potent growth factor for ER-α-positive human breast cancer
A. Kate Sasser , Nicholas J. Sullivan , Adam W. Studebaker , Lindsay F. Hendey , Amy E. Axel , and Brett M. Hall
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, Volume 21 (13): 3763
Fed of American Socs for Experimental Biology – Nov 1, 2007
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