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.
|Number of pages||7|
|Publication status||Published - 01-01-2002|
All Science Journal Classification (ASJC) codes
- Cancer Research