Osteonectin/SPARC induction by ectopic β3 integrin in human radial growth phase primary melanoma cells

Richard A. Sturm, Kapaeth Satyamoorthy, Bhavesh Vaidya, Meenhard Herlyn, Richard A. Sturm, Brooke B. Gardiner, Darren J. Smit, Freidegund Meier

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    50 Citations (Scopus)

    Abstract

    Expression of the β3 integrin subunit in melanoma in situ has been found to correlate with tumor thickness, the ability to invade and metastasize, and poor prognosis. Transition from the radial growth phase (RGP) to the vertical growth phase (VGP) is a critical step in melanoma progression and survival and is distinguished by the expression of β3 integrin. The molecular pathways that operate in melanoma cells associated with invasion and metastasis were examined by ectopic induction of the β3 integrin subunit in RGP SBc12 and WM1552C melanoma cells, which converts these cells to a VGP phenotype. We used cDNA representational difference analysis subtractive hybridization between β3-positive and -negative melanoma cells to assess gene expression profile changes accompanying RGP to VGP transition. Fourteen fragments from known genes including osteonectin (also known as SPARC and BM-40) were identified after three rounds of representational difference analysis. Induction of osteonectin was confirmed by Northern and Western blot analysis and immunohistochemistry and correlated in organotypic cultures with the β3-induced progression from RGP to VGP melanoma. Expression of osteonectin was also associated with reduced adhesion to vitronectin, but not to fibronectin. Osteonectin expression was not blocked when melanoma cells were cultured with anti-αvβ3 LM609 mAb, mitogenactivated protein kinase, or protein kinase C inhibitors, indicating that other signaling pathway(s) operate through αv3 integrin during conversion from RGP to VGP.

    Original languageEnglish
    Pages (from-to)226-232
    Number of pages7
    JournalCancer Research
    Volume62
    Issue number1
    Publication statusPublished - 01-01-2002

    All Science Journal Classification (ASJC) codes

    • Oncology
    • Cancer Research

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