Mel-CAM-specific genetic suppressor elements inhibit melanoma growth and invasion through loss of gap junctional communication

Kapaettu Satyamoorthy, Joep Muyrers, Friedegund Meier, Dipa Patel, Meenhard Herlyn

    Research output: Contribution to journalArticle

    67 Citations (Scopus)

    Abstract

    Normal human melanocytes are interspersed singly among keratinocytes along the basement membrane of the epidermis, whereas melanoma cells readily adhere to each other during invasion of the dermis or distant organs. The tumorigenic and metastatic phenotype of melanoma cells often correlates with increased expression of cell-cell and cell-matrix adhesion receptors. Mel-CAM (MCAM, MUC 18, CD146) is a cell-cell adhesion receptor highly expressed by melanoma cells but not normal melanocytes. We show here that inhibition of Md-CAM expression in metastatic melanoma cells using genetic suppressor elements of Mel-CAM cDNA leads to inhibition of adhesion between melanoma cells and to downregulation of the tumorigenic phenotype. Growth was not inhibited in genetic suppressor elements-transduced melanoma cells cultured in monolayers but was inhibited when cells were maintained anchorage-independently in soft agar and greatly reduced in immunodeficient mice. A three-dimensional epidermal skin equivalent model demonstrated that Mel-CAM allows melanoma cells to separate from the epidermis and invade the basement membrane zone and dermis. However, melanoma cells with little or no Mel-CAM were poorly invasive, possibly due to their loss of gap junctional communication. These results suggest the multifunctional role of a melanoma-associated cell-cell adhesion receptor in tumor progression.

    Original languageEnglish
    Pages (from-to)4676-4684
    Number of pages9
    JournalOncogene
    Volume20
    Issue number34
    DOIs
    Publication statusPublished - 02-08-2001

    All Science Journal Classification (ASJC) codes

    • Molecular Biology
    • Genetics
    • Cancer Research

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