Emergence of undifferentiated rat tracheal cell carcinomas, but not squamous cell carcinomas, is associated with a loss of expression of E-cadherin and of gap junction communication.
A series of cells representing normal, non-tumorigenic cell lines, as well as differentiating neoplastic and undifferentiated neoplastic rat tracheal epithelial cell populations were evaluated for their ability to establish homologous and/or heterologous cell-cell gap junction communication in culture. Gap junction communication was evaluated by flow cytometric quantitation of the transfer of the fluorescent dye calcein from a donor to a recipient cell population via gap junctions. The data indicate that normal primary cultures of rat tracheal epithelial cells, as well as non-tumorigenic cell lines and squamous cell carcinomas cell populations, retain the ability to establish both homologous and heterologous gap junction communication. In all cases an average of >48% of recipient cells had acquired calcein label during a 5-h interval of co-culture of donor and recipient cells at confluent densities. Cells harvested directly from squamous cell carcinoma tumors exhibited similar levels of cell-cell communication. In contrast, cells giving rise to undifferentiated carcinomas, as well as cells harvested from undifferentiated carcinomas, exhibited very low levels or no homologous or heterologous cell-cell communication. Cell populations exhibiting distinctly different communication phenotypes were evaluated by Northern blot analysis for expression of connexins (Cx 26, 32 and 43) and E-cadherin. Neither communicating nor non-communicating cells expressed connexin 32. Those cell populations, which established functional gap junctions, expressed E-cadherin as well as connexin 26 and/or 43. In contrast, those cell populations that lacked the ability to communicate universally lacked expression of E-cadherin, and a quarter also lacked expression of detectable levels of connexin.
Terzaghi-Howe
M
M
Oak Ridge National Laboratory, Life Sciences Division, TN 37831-8080, USA.
Chang
G W
GW
Popp
D
D
D000818:Animals; D015820:Cadherins / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000209:etiology* / Q000648:ultrastructure; D002450:Cell Communication; D017630:Connexins / Q000032:analysis; D004847:Epithelial Cells / Q000648:ultrastructure; D017629:Gap Junctions / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D010641:Phenotype; D051381:Rats; D011916:Rats, Inbred F344; D014134:Tracheal Neoplasms / Q000737:chemistry / Q000209:etiology* / Q000648:ultrastructure
D015820:Cadherins; D017630:Connexins