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Tumor-derived mesenchymal stem cells and orthotopic site increase the tumor initiation potential of putative mouse mammary cancer stem cells derived from MMTV-PyMT mice

  • Research Article
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Tumor Biology

Abstract

The ability to transplant mammary cancer stem cells, identified by the phenotype CD24+CD29+CD49f+Sca-1low, is dependent on the microenvironment in which the cells are placed. Using the MMTV-PyMT mouse model of mammary cancer, we now report two methods of tumor growth enhancement: contributions of tumor stroma in the form of tumor-derived mesenchymal stem cells and orthotopic vs. heterotopic transplantation sites. To support evidence of stem cell function, tumor-derived mesenchymal stem cells differentiated into adipocyte- and osteocyte-like cells after culture in specific medium. Co-injection of tumor-initiating cells with tumor-derived mesenchymal stem cells significantly increased tumor initiation compared to subcutaneous injection of TICs alone; co-injection also allowed tumor initiation with a single TIC. Interestingly, we observed the formation of sarcomas after co-injections of tumor-derived mesenchymal stem cells or mouse embryonic fibroblasts with TICs; sarcomas are not observed in spontaneous MMTV-PyMT tumors and rarely observed in injections of TICs alone. Tumor initiation was also significantly increased in the orthotopic injection site compared to heterotopic injections. We conclude that tumor stroma and orthotopic sites both enhance tumor initiation by mammary cancer stem cells.

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Abbreviations

BM:

Bone marrow

CFP:

Cleared mammary fat pad

CSC:

Cancer stem cell

FMMC:

Female mouse mammary cancer cell line

FVB/N:

Friend Virus B NIH mouse strain

MCF7:

Michigan Cancer Foundation cell line 7

MEFs:

Mouse embryonic fibroblasts

MMMC:

Male mouse mammary cancer cell line

MMTV-PyMT:

Mouse mammary tumor virus promoter–Polyoma middle T-antigen

MSCs:

Mesenchymal stem cells

SC:

Subcutaneous

SDF-1:

Stromal derived factor 1

TDMSCs:

Tumor-derived mesenchymal stem cells

TGF-β:

Tumor growth factor beta

TI:

Tumor initiation

TICs:

Tumor-initiating cells

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Acknowledgments

This work was supported by NIH R01 CA 112481 (Dr. Sell) and the Ordway Research Institute (Dr. Glinsky).

Conflicts of interest

None

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Authors and Affiliations

  1. Translational and Functional Genomics Laboratory, Ordway Research Institute, Albany, NY, 12208, USA

    Denise Grant Lanza, Jun Ma, Anna Glinskii & Gennadi Glinsky

  2. Laboratory of Adult and Cancer Stem Cells, Ordway Research Institute, Albany, NY, 12208, USA

    Denise Grant Lanza, Jun Ma, Ian Guest & Stewart Sell

  3. Ordway Cancer Center & Flow Cytometry Core Facility, Ordway Research Institute, Albany, NY, 12208, USA

    Chang Uk-Lim

  4. Wadsworth Center, New York State Department of Health, University at Albany, State University of New York, Albany, NY, 12201, USA

    Stewart Sell

  5. Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY, 12201, USA

    Denise Grant Lanza & Stewart Sell

  6. Department of Pathology & Laboratory Medicine, Albany Medical College, Albany, NY, 12208, USA

    Gennadi Glinsky

  7. Division of Urology, Department of Surgery, Albany Medical College, Albany, NY, 12208, USA

    Gennadi Glinsky

Authors
  1. Denise Grant Lanza
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  2. Jun Ma
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  3. Ian Guest
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  4. Chang Uk-Lim
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  5. Anna Glinskii
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  7. Stewart Sell
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Correspondence to Stewart Sell.

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Lanza, D.G., Ma, J., Guest, I. et al. Tumor-derived mesenchymal stem cells and orthotopic site increase the tumor initiation potential of putative mouse mammary cancer stem cells derived from MMTV-PyMT mice. Tumor Biol. 33, 1997–2005 (2012). https://doi.org/10.1007/s13277-012-0459-3

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  • DOI: https://doi.org/10.1007/s13277-012-0459-3

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