Cancer Stem Cells

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Identification of Vitronectin as an Extrinsic Inducer of Cancer Stem Cell Differentiation and Tumor Formation†

  1. Elaine M. Hurt1,‡,*,
  2. King Chan2,
  3. Maria Ana Duhagon Serrat1,4,
  4. Suneetha B. Thomas3,
  5. Timothy D. Veenstra2,
  6. William L. Farrar1

Article first published online: 8 DEC 2009

DOI: 10.1002/stem.271

Issue

STEM CELLS

STEM CELLS

Volume 28, Issue 3, pages 390–398, March 2010

Additional Information

How to Cite

Hurt, E. M., Chan, K., Duhagon Serrat, M. A., Thomas, S. B., Veenstra, T. D. and Farrar, W. L. (2010), Identification of Vitronectin as an Extrinsic Inducer of Cancer Stem Cell Differentiation and Tumor Formation. STEM CELLS, 28: 390–398. doi: 10.1002/stem.271

Author Information

  1. 1

    Cancer Stem Cell Section, Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, USA

  2. 2

    Laboratory of Proteomics and Analytical Technologies, National Cancer Institute, Frederick, Maryland, USA

  3. 3

    Basic Research Program, Science Applications International Corporation-Frederick, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, USA

  4. 4

    LIM-F. Ciencias, Genetica-F. Medicina, Universidad de la República, Montevideo, Uruguay

  1. ‡

    Telephone: (301) 846-6867; Fax: (301) 846-6104

*Laboratory of Cancer Prevention, NCI-Frederick, 1050 Boyles Street, Building 560, Room 21-81

  1. †

    Author contributions: E.H.: Conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing; K.C.: Conception and design, collection and assembly of data, manuscript writing; M.A.D.S.: Provision of study materials, collection of data; S.T.: Collection of data; T.V.: Conception and design, financial support; W.F.: Conception and design, financial support, final approval of manuscript.

Publication History

  1. Issue published online: 24 MAR 2010
  2. Article first published online: 8 DEC 2009
  3. Accepted manuscript online: 8 DEC 2009 12:00AM EST
  4. Manuscript Accepted: 30 NOV 2009
  5. Manuscript Received: 20 JUL 2009

Funded by

  • National Cancer Institute, NIH. Grant Number: N01-CO-12400
  • Intramural Research Program of the NIH
  • National Cancer Institute
  • Center for Cancer Research

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Keywords:

  • Prostate cancer;
  • Breast cancer;
  • Tumor-initiating;
  • Vitronectin;
  • Arginine-glycine-aspartic acid peptide;
  • Integrin alphaVbeta3

Abstract

There is mounting evidence that tumors are initiated by a rare subset of cells called cancer stem cells (CSCs). CSCs are generally quiescent, self-renew, form tumors at low numbers, and give rise to the heterogeneous cell types found within a tumor. CSCs isolated from multiple tumor types differentiate both in vivo and in vitro when cultured in serum, yet the factors responsible for their differentiation have not yet been identified. Here we show that vitronectin is the component of human serum driving stem cell differentiation through an integrin αVβ3-dependent mechanism. CSCs cultured on vitronectin result in downregulation of stem cell genes, modulation of differentiation markers, and loss of β-catenin nuclear localization. Blocking integrin αVβ3 inhibits differentiation and subsequently tumor formation. Thus, CSCs must be engaged by one or more extracellular signals to differentiate and initiate tumor formation, defining a new axis for future novel therapies aimed at both the extrinsic and intracellular pathways. STEM CELLS 2010;28:390–398

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