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Tumor Biology

, Volume 33, Issue 6, pp 1997–2005 | Cite as

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

  • Denise Grant Lanza
  • Jun Ma
  • Ian Guest
  • Chang Uk-Lim
  • Anna Glinskii
  • Gennadi Glinsky
  • Stewart Sell
Research Article

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.

Keywords:

Tumor-derived mesenchymal cells MMTV-PyMT Tumor initiation Stroma Sarcoma 

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

Notes

Acknowledgments

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

Conflicts of interest

None

Supplementary material

13277_2012_459_MOESM1_ESM.pdf (741 kb)
ESM 1 (PDF 740 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  • Denise Grant Lanza
    • 1
    • 2
    • 5
  • Jun Ma
    • 1
    • 2
  • Ian Guest
    • 2
  • Chang Uk-Lim
    • 3
  • Anna Glinskii
    • 1
  • Gennadi Glinsky
    • 1
    • 6
    • 7
  • Stewart Sell
    • 2
    • 4
    • 5
  1. 1.Translational and Functional Genomics LaboratoryOrdway Research InstituteAlbanyUSA
  2. 2.Laboratory of Adult and Cancer Stem CellsOrdway Research InstituteAlbanyUSA
  3. 3.Ordway Cancer Center & Flow Cytometry Core FacilityOrdway Research InstituteAlbanyUSA
  4. 4.Wadsworth Center, New York State Department of HealthUniversity at Albany, State University of New YorkAlbanyUSA
  5. 5.Department of Biomedical Sciences, School of Public HealthUniversity at Albany, State University of New YorkAlbanyUSA
  6. 6.Department of Pathology & Laboratory MedicineAlbany Medical CollegeAlbanyUSA
  7. 7.Division of Urology, Department of SurgeryAlbany Medical CollegeAlbanyUSA

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