HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: fj.07-8832comv1 21/13/3763    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sasser, A. K. Articles by Hall, B. M. Search for Related Content PubMed PubMed Citation Articles by Sasser, A. K. Articles by Hall, B. M.

Interleukin-6 is a potent growth factor for ER--positive human breast cancer

A. Kate Sasser^*, Nicholas J. Sullivan^*, Adam W. Studebaker, Lindsay F. Hendey, Amy E. Axel and Brett M. Hall^*,

^* Integrated Biomedical Science Graduate Program, Department of Pediatrics, School of Medicine & Public Health, The Ohio State University, Columbus, Ohio, USA; and

Center for Childhood Cancer, Children’s Research Institute, Columbus, Ohio, USA

¹Correspondence: Center for Childhood Cancer, WA5015, Children’s Research Institute, 700 Children’s Dr., Columbus, OH 43205, USA. E-mail: hallb{at}ccri.net

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 fibroblast 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-75–1) 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 the ER-positive mammary tumor cell line MCF-7 after paracrine and autocrine IL-6 exposure, where MCF-7 growth rates were enhanced by >2-fold when cocultured with MSC in vitro and even more pronounced in vivo with autocrine IL-6 production.—Sasser, A. K., Sullivan, N. J., Studebaker, A. W., Hendey, L. F., Axel, A. E., Hall, B. M. Interleukin-6 is a potent growth factor for ER--positive human breast cancer.

Key Words: tumor microenvironment • IL-6 • metastasis • mesenchymal stem cells • ER-alpha • STAT3 • MSC

This article has been cited by other articles:

				A. W. Studebaker, G. Storci, J. L. Werbeck, P. Sansone, A. K. Sasser, S. Tavolari, T. Huang, M. W.Y. Chan, F. C. Marini, T. J. Rosol, et al. Fibroblasts Isolated from Common Sites of Breast Cancer Metastasis Enhance Cancer Cell Growth Rates and Invasiveness in an Interleukin-6-Dependent Manner Cancer Res., November 1, 2008; 68(21): 9087 - 9095. [Abstract] [Full Text] [PDF]

				G. Lazennec and C. Jorgensen Concise Review: Adult Multipotent Stromal Cells and Cancer: Risk or Benefit? Stem Cells, June 1, 2008; 26(6): 1387 - 1394. [Abstract] [Full Text] [PDF]

				B. D. Hollingshead, T. V. Beischlag, B. C. DiNatale, P. Ramadoss, and G. H. Perdew Inflammatory Signaling and Aryl Hydrocarbon Receptor Mediate Synergistic Induction of Interleukin 6 in MCF-7 Cells Cancer Res., May 15, 2008; 68(10): 3609 - 3617. [Abstract] [Full Text] [PDF]