Connexin transfection induces invasive properties in HeLa cells

Gap-junctional coupling of tumor cells facilitates their invasion into normal tissue as was further investigated with connexin-transfected HeLa cells by an in vitro assay. Wild-type HeLa cells are coupling deficient and did not show invasive properties when multicell spheroids were confronted with precultured embryonic chicken heart fragments. After transfection with cDNA of Cx31, Cx40, or Cx43, these cells were homotypically coupled; Cx40- and Cx43-transfected HeLa cells also were heterotypically coupled with embryonic chicken heart cells in monolayer coculture. Transfected clones revealed invasive properties in the chicken heart in vitro assay. However, the pattern of invasion differed between these transfectants: After 4 days Cx43-transfected HeLa cells were found in the central part of heart spheroids; Cx40- and Cx31-transfected HeLa cells, however, did not invade the central core but were detected in the outer part of heart spheroids. We conclude that connexin expression supports invasion of tumor cells into normal tissue, but heterotypic gap-junctional coupling is not required for this process.