White adipose tissue cells are recruited by experimental tumors and promote cancer progression in mouse models

Yan Zhang, Alexes Daquinag, Dmitry Traktuev, Felipe Amaya-Manzanares, Paul J. Simmons, Keith L. March, Renata Pasqualini, Wadih Arap, Mikhail G. Kolonin

Research output: Contribution to journalArticle

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Abstract

The connection between obesity and accelerated cancer progression has been established, but the mediating mechanisms are not well understood. We have shown that stromal cells from white adipose tissue (WAT) cooperate with the endothelium to promote blood vessel formation through the secretion of soluble trophic factors. Here, we hypothesize that WAT directly mediates cancer progression by serving as a source of cells that migrate to tumors and promote neovascularization. To test this hypothesis, we have evaluated the recruitment of WAT-derived cells by tumors and the effect of their engraftment on tumor growth by integrating a transgenic mouse strain engineered for expansion of traceable cells with established allograft and xenograft cancer models. Our studies show that entry of adipose stromal and endothelial cells into systemic circulation leads to their homing to and engraftment into tumor stroma and vasculature, respectively. We show that recruitment of adipose stromal cells by tumors is sufficient to promote tumor growth. Finally, we show that migration of stromal and vascular progenitor cells from WAT grafts to tumors is also associated with acceleration of cancer progression. These results provide a biological insight for the clinical association between obesity and cancer, thus outlining potential avenues for preventive and therapeutic strategies.

Original languageEnglish
Pages (from-to)5259-5266
Number of pages8
JournalCancer Research
Volume69
Issue number12
DOIs
StatePublished - Jun 15 2009

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White Adipose Tissue
Neoplasms
Stromal Cells
Blood Vessels
Obesity
Growth
Heterografts
Transgenic Mice
Endothelium
Allografts
Stem Cells
Endothelial Cells

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Zhang, Y., Daquinag, A., Traktuev, D., Amaya-Manzanares, F., Simmons, P. J., March, K. L., ... Kolonin, M. G. (2009). White adipose tissue cells are recruited by experimental tumors and promote cancer progression in mouse models. Cancer Research, 69(12), 5259-5266. https://doi.org/10.1158/0008-5472.CAN-08-3444

White adipose tissue cells are recruited by experimental tumors and promote cancer progression in mouse models. / Zhang, Yan; Daquinag, Alexes; Traktuev, Dmitry; Amaya-Manzanares, Felipe; Simmons, Paul J.; March, Keith L.; Pasqualini, Renata; Arap, Wadih; Kolonin, Mikhail G.

In: Cancer Research, Vol. 69, No. 12, 15.06.2009, p. 5259-5266.

Research output: Contribution to journalArticle

Zhang, Y, Daquinag, A, Traktuev, D, Amaya-Manzanares, F, Simmons, PJ, March, KL, Pasqualini, R, Arap, W & Kolonin, MG 2009, 'White adipose tissue cells are recruited by experimental tumors and promote cancer progression in mouse models', Cancer Research, vol. 69, no. 12, pp. 5259-5266. https://doi.org/10.1158/0008-5472.CAN-08-3444
Zhang, Yan ; Daquinag, Alexes ; Traktuev, Dmitry ; Amaya-Manzanares, Felipe ; Simmons, Paul J. ; March, Keith L. ; Pasqualini, Renata ; Arap, Wadih ; Kolonin, Mikhail G. / White adipose tissue cells are recruited by experimental tumors and promote cancer progression in mouse models. In: Cancer Research. 2009 ; Vol. 69, No. 12. pp. 5259-5266.
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