Experimental coexpression of vimentin and keratin intermediate filaments in human melanoma cells augments motility

Yi Wen Chu, Elisabeth A. Seftor, Lewis H. Romer, Mary J.C. Hendrix*

*Corresponding author for this work

Research output: Contribution to journalArticle

121 Scopus citations

Abstract

Intermediate filaments have been used as cell-type-specific markers in differentiation and pathology; however, recent reports have demonstrated the coexpression of vimentin (a mesenchymal marker) and keratins (epithelial markers) in numerous neoplasms, including melanoma, which has been linked to metastatic disease. To test the hypothesis that coexpression of vimentin and keratins by melanoma cells contributes to a more migratory and invasive phenotype, we co-transfected a vimentin-positive human melanoma cell line, A375P (of low invasive ability), with cDNAs for keratins 8 and 18. The resultant stable transfectants expressed vimentin- and keratin-positive intermediate filaments and showed a two- to threefold increase in their invasion of basement membrane matrix and migration through gelatin in vitro. These findings were further corroborated by video cinematography. During attachment and spreading on fibronectin, the transfectants containing vimentin and keratins 8 and 18 demonstrated an increase in focal adhesions that stained positive for β1 integrin and phosphotyrosine, along with enhanced membrane ruffling and actin stress fiber formation. From these data, we postulate that coexpression of vimentin and keratins results in increased cytoskeletal interactions at focal contacts within extracellular matrices involving integrin cell signaling events, which contributes to a more migratory behavior.

Original languageEnglish (US)
Pages (from-to)63-69
Number of pages7
JournalAmerican Journal of Pathology
Volume148
Issue number1
StatePublished - Jan 1996

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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