Gap-junctional coupling of tumor cells facilitates their invasion into
normal tissue as was further investigated with connexin-transfected H
eLa cells by an in vitro assay. Wild-type HeLa cells are coupling defi
cient and did not show invasive properties when multicell spheroids we
re confronted with precultured embryonic chicken heart fragments. Afte
r transfection with cDNA of Cx31, Cx40, or Cx43, these cells were homo
-typically coupled; Cx40- and Cx43-transfected HeLa cells also were he
terotypically coupled with embryonic chicken heart cells in monolayer
coculture. Transfected clones revealed invasive properties in the chic
ken heart in vitro assay. However, the pattern of invasion differed be
tween these transfectants: After 4 days Cx43-transfected HeLa cells we
re found in the central part of heart spheroids; Cx40- and Cx31-transf
ected HeLa cells, however, did not invade the central core but were de
tected in the outer part of heart spheroids. We conclude that connexin
expression supports invasion of tumor cells into normal tissue, but h
eterotypic gap-junctional coupling is not required for this process. (
C) 1998 Academic Press.