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Mechanism of anchorage-independency and tumor formation of cancer cells: possible involvement of cell membrane–bound laminin-332

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Abstract

Cancer cells are characterized by anchorage-independency and tumor formation. Involvement of laminin-332 in the pathogenesis of cancer has also been reported. I present a theory that can explain these characteristics together. Proliferating keratinocytes in wound healing produce and deposit laminin-332, which is shown in the provisional basement membrane of a wound. In association with wound closure, expression of LG4/5 domain on the α3 chain of laminin-332 disappears, implicating cleavage of LG4/5 domain. LG4/5 domain expression indicates that laminin-332 prior to the cleavage is bound to the cell membrane, because LG4/5 domain is a cell binding site. In this binding, heparan sulfate proteoglycan on the cell surface seems to be the acceptor for LG4/5 domain. I named this laminin “cell membrane–bound laminin-332” (ML332). ML332 would then bind to integrin α3β1 via LG1-3 domain, the integrin binding site, and activate FAK and the following Ras/MAPK pathway. Therefore, ML332 eliminates the need for proliferating keratinocytes to bind to processed laminin-332 secreted and deposited into the basement membrane for their proliferation (anchorage-independency). This may hold true of every proliferating epithelial cell, either benign or malignant. Whereas wound closure deprives keratinocytes of anchorage-independency, such events do not occur in cancer cells, and cancer cells maintain anchorage-independency. In the basement membrane formation by epithelial cells, short arms of laminin-332 anchored to the cell membrane bind each other and generate a meshwork polymer. This is the three-arm interaction model. In a similar manner, short-arm interactions between adjacent cancer cells may occur and induce tumor formation.

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  1. Katayama Dermatology Clinic, Omotecho 1-25-12, Maebashi, Gunma, 371-0024, Japan

    Hiroshi Katayama

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  1. Hiroshi Katayama
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Correspondence to Hiroshi Katayama.

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Katayama, H. Mechanism of anchorage-independency and tumor formation of cancer cells: possible involvement of cell membrane–bound laminin-332. Cell Tissue Res 379, 255–259 (2020). https://doi.org/10.1007/s00441-019-03114-7

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  • DOI: https://doi.org/10.1007/s00441-019-03114-7

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