Breast Cancer Research and Treatment

, Volume 121, Issue 2, pp 293–300

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

Authors

  • Lyndsay V. Rhodes
    • Department of Medicine, Section of Hematology & Medical OncologyTulane University Health Sciences Center
  • Shannon E. Muir
    • Department of Medicine, Section of Hematology & Medical OncologyTulane University Health Sciences Center
  • Steven Elliott
    • Department of Medicine, Section of Hematology & Medical OncologyTulane University Health Sciences Center
  • Lori M. Guillot
    • Department of Medicine, Section of Hematology & Medical OncologyTulane University Health Sciences Center
  • James W. Antoon
    • Department of PharmacologyTulane University Health Sciences Center
  • Patrice Penfornis
    • The Center for Gene TherapyTulane University Health Sciences Center
  • Syreeta L. Tilghman
    • Department of Pulmonary Diseases Critical Care and Environmental MedicineTulane University Health Sciences Center
  • Virgilio A. Salvo
    • Department of Medicine, Section of Hematology & Medical OncologyTulane University Health Sciences Center
  • Juan P. Fonseca
    • Department of Medicine, Section of Hematology & Medical OncologyTulane University Health Sciences Center
  • Michelle R. Lacey
    • Department of MathematicsTulane University
  • Barbara S. Beckman
    • Department of Pharmacology, The Center for Bioenvironmental Research, The Tulane Cancer CenterTulane University Health Sciences Center
  • John A. McLachlan
    • Department of Pharmacology, The Center for Bioenvironmental Research, The Tulane Cancer CenterTulane University Health Sciences Center
  • Brian G. Rowan
    • Department of Structural and Cellular Biology, The Tulane Cancer CenterTulane University Health Sciences Center
  • Radhika Pochampally
    • The Center for Gene Therapy, Department of PharmacologyTulane University Health Sciences Center
    • Department of Medicine, Section of Hematology & Medical Oncology, The Center for Bioenvironmental Research, The Tulane Cancer CenterTulane University Health Sciences Center
Preclinical study

DOI: 10.1007/s10549-009-0458-2

Cite this article as:
Rhodes, L.V., Muir, S.E., Elliott, S. et al. Breast Cancer Res Treat (2010) 121: 293. doi:10.1007/s10549-009-0458-2

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.

Keywords

Mesenchymal stem cellsBreast carcinomaProgesterone receptorStromal-derived factor 1Tumor microenvironment

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

Supplementary material

10549_2009_458_MOESM1_ESM.pdf (32 kb)
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)

Copyright information

© Springer Science+Business Media, LLC. 2009