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Adult human mesenchymal stem cells enhance breast tumorigenesis and promote hormone independence

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Abstract

Adult human mesenchymal stem cells (hMSCs) have been shown to home to sites of breast cancer and integrate into the tumor stroma. We demonstrate here the effect of hMSCs on primary breast tumor growth and the progression of these tumors to hormone independence. Co-injection of bone marrow-derived hMSCs enhances primary tumor growth of the estrogen receptor-positive, hormone-dependent breast carcinoma cell line MCF-7 in the presence or absence of estrogen in SCID/beige mice. We also show hormone-independent growth of MCF-7 cells when co-injected with hMSCs. These effects were found in conjunction with increased immunohistochemical staining of the progesterone receptor in the MCF-7/hMSC tumors as compared to MCF-7 control tumors. This increase in PgR expression indicates a link between MCF-7 cells and MSCs through ER-mediated signaling. Taken together, our data reveal the relationship between tumor microenvironment and tumor growth and the progression to hormone independence. This tumor stroma-cell interaction may provide a novel target for the treatment of estrogen receptor-positive, hormone-independent, and endocrine-resistant breast carcinoma.

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Abbreviations

hMSC(s):

Human mesenchymal stem cell(s)

FFPE:

Formalin-fixed paraffin-embedded

PgR:

Progesterone receptor

ER:

Estrogen receptor

DMEM:

Dulbecco’s modified eagle medium

PBS:

Phosphate-buffered saline

EDTA:

Ethylenediaminetetraacetic acid

H&E:

Hematoxylin and eosin

SCID:

Severe combined immunodeficiency

SDF-1:

Stromal-derived factor 1

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Acknowledgments

We thank Melyssa Bratton, Ph.D. and Erica Nierth-Simpson, Ph.D. for technical advice and manuscript revision. We also thank the Histology and Pathology laboratory, Tulane University School of Medicine for their IHC expertise. This work was supported in part by the Department of Defense Breast Cancer Research Program (54551G1).

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Correspondence to Matthew E. Burow.

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10549_2009_458_MOESM1_ESM.pdf

MCF-7 Xenograft model showing delayed Estrogen response. Tumor volume in mm3 (mean ± s.e.m.). 4-6-week-old female ovariectomized SCID/beige mice were injected subcutaneously with 1x106 MCF-7 in 50μl of sterile PBS with 100 μl reduced growth factor matrigel (BD biosystems), n = 5 mice per group. All animals in the estrogen group were implanted with a 0.72mg 60-day time-release estrogen pellet (Innovative Research of America) subcutaneously in neck. Tumors were measured every 7-10 days, (*, p<0.05; **, p<0.001) (PDF 31 kb)

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Rhodes, L.V., Muir, S.E., Elliott, S. et al. Adult human mesenchymal stem cells enhance breast tumorigenesis and promote hormone independence. Breast Cancer Res Treat 121, 293–300 (2010). https://doi.org/10.1007/s10549-009-0458-2

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  • DOI: https://doi.org/10.1007/s10549-009-0458-2

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