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Microenvironment and Immunology

Stromal Progenitor Cells from Endogenous Adipose Tissue Contribute to Pericytes and Adipocytes That Populate the Tumor Microenvironment

Yan Zhang, Alexes C. Daquinag, Felipe Amaya-Manzanares, Olga Sirin, Chieh Tseng and Mikhail G. Kolonin
Yan Zhang
Center for Stem Cell and Regenerative Medicine, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas
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Alexes C. Daquinag
Center for Stem Cell and Regenerative Medicine, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas
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Felipe Amaya-Manzanares
Center for Stem Cell and Regenerative Medicine, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas
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Olga Sirin
Center for Stem Cell and Regenerative Medicine, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas
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Chieh Tseng
Center for Stem Cell and Regenerative Medicine, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas
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Mikhail G. Kolonin
Center for Stem Cell and Regenerative Medicine, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas
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DOI: 10.1158/0008-5472.CAN-12-0294 Published October 2012
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Abstract

Epidemiologic studies associate cancer with obesity, but the pathophysiologic connections remain obscure. In this study, we show that obesity facilitates tumor growth in mice irrespective of concurrent diet, suggesting a direct effect of excess white adipose tissue (WAT). When transplanted into mice, adipose stromal cells (ASC) can serve as perivascular adipocyte progenitors that promote tumor growth, perhaps helping explain the obesity–cancer link. In developing this hypothesis, we showed that ASCs are expanded in obesity and that they traffic from endogenous WAT to tumors in several mouse models of cancer. Strikingly, a comparison of circulating and tumor-infiltrating cell populations in lean, and obese mice revealed that cancer induces a six-fold increase of ASC frequency in the systemic circulation. We obtained evidence that ASCs mobilized in this way can be recruited into tumors, where they can be incorporated into blood vessels as pericytes and they can differentiate into adipocytes in an obesity-dependent manner. Extending this evidence, we found that increased tumor vascularization (reflected by changes in tumor vascular morphology and a two-fold increase in vascular density) was associated with intratumoral adipocytes and elevated proliferation of neighboring malignant cells. Taken together, our results suggest that ASCs recruited from endogenous adipose tissue can be recruited by tumors to potentiate the supportive properties of the tumor microenvironment. Cancer Res; 72(20); 5198–208. ©2012 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).

  • Received January 25, 2012.
  • Revision received August 13, 2012.
  • Accepted August 17, 2012.
  • ©2012 American Association for Cancer Research.

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Cancer Research: 72 (20)
October 2012
Volume 72, Issue 20
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Stromal Progenitor Cells from Endogenous Adipose Tissue Contribute to Pericytes and Adipocytes That Populate the Tumor Microenvironment
Yan Zhang, Alexes C. Daquinag, Felipe Amaya-Manzanares, Olga Sirin, Chieh Tseng and Mikhail G. Kolonin
Cancer Res October 15 2012 (72) (20) 5198-5208; DOI: 10.1158/0008-5472.CAN-12-0294

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Stromal Progenitor Cells from Endogenous Adipose Tissue Contribute to Pericytes and Adipocytes That Populate the Tumor Microenvironment
Yan Zhang, Alexes C. Daquinag, Felipe Amaya-Manzanares, Olga Sirin, Chieh Tseng and Mikhail G. Kolonin
Cancer Res October 15 2012 (72) (20) 5198-5208; DOI: 10.1158/0008-5472.CAN-12-0294
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