Pharmaceutical Sciences Faculty Publications

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

Document Type

Article

Publication Date

3-31-2010

Journal Title

Stem Cells

ISSN

1549-4918

Volume

28

Issue

3

First Page

390

Last Page

398

DOI

10.1002/stem.271

PubMed ID

19998373

PubMed Central® ID

PMC3448441

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 alpha V beta 3-dependent mechanism. CSCs cultured on vitronectin result in downregulation of stem cell genes, modulation of differentiation markers, and loss of beta-catenin nuclear localization. Blocking integrin alpha V beta 3 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.

Keywords

Biomarkers, blood proteins, breast neoplasms, carcinoma, cell differentiation, tumor, chromatography, mass spectrometry, neoplasms, vitronectin

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