Osteopontin regulates multiple functions contributing to human colon cancer development and progression

R. B. Irby, S. M. McCarthy, T. J. Yeatman

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

Osteopontin (OPN) is a secreted phosphoglycoprotein known to interact with a number of integral receptors. While increased OPN expression has been reported in a number of human cancers, and its cognate receptors (αv-β3, αv-β5, and αv-β1 integrins and CD44) have been identified, its role in colon cancer development and progression has not been extensively studied. We previously identified, using a combination of gene expression and tissue microarrays, that increased OPN expression is concordant with tumor stage. The current study examined the functional role of OPN in colon cancer progression and metastatic potential. The principal findings of this study were that both endogenous OPN expression (via stable transfection) as well as exogenous OPN (added to culture medium) enhanced the motility and invasive capacity of human colon cancer cells in vitro. OPN appeared to regulate motility though interaction with CD44. OPN expression also reduced intercellular (homotypic) adhesion, an important characteristic of metastatic cancer cells. Stable transfection of four poorly tumorigenic human colon cancer cell lines with OPN also resulted in enhanced tumorigenicity in vivo with increased proliferation and increased CD31 positive microvessel counts, concordant with the degree of OPN expression. Collectively, these results suggest that OPN may affect multiple functional components contributing to human colon cancer progression and solidifies its role in this process.

Original languageEnglish (US)
Pages (from-to)515-523
Number of pages9
JournalClinical and Experimental Metastasis
Volume21
Issue number6
DOIs
StatePublished - Oct 1 2004

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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