Increased cell-substratum adhesion, and decreased gelatinase secretion and cell growth, induced by E-cadherin transfection of human colon carcinoma cells.
Metastasis of colon carcinomas is assumed to be caused by multiple steps, which include a loss of cell adhesion that results in the release of carcinoma cells from the original tumor tissue. A human colon carcinoma cell line COKFu was established from a poorly differentiated metastatic adenocarcinoma without cell-cell adhesion and without expression of E-cadherin mRNA and protein. This cell line was co-transfected with mouse E-cadherin cDNA in an expression vector and a neomycin-resistant gene. The parental carcinoma cells had a spindle shape and were scattered, whereas the transfected cells, which expressed exogenous E-cadherin gene, showed a more compact shape with strong cell-cell adhesion and with increased adhesiveness to collagen gel. These cells showed a significantly low anchorage independency (2-7%) and decreased invasiveness (30%) compared to the parental cells. Growth rate of transfectants was decreased both in vitro and in the subcutis of nude mice, with decreased lymphnode metastasis in the case of intravenous injection. It was additionally found that activity of 62 kd gelatinase, secreted from parental cells, was lost or decreased in E-cadherin-transfected cells. These results suggest that E-cadherin is not only involved in the cell-cell adhesion of colon carcinomas, it also has a wider effect, including cell-substratum adhesion and the regulation of proteinase secretion from the cells, resulting in partial suppression of invasiveness and tumorigenic growth.
Department of Biochemistry, Tokyo Metropolitan Institute of Medical Science, Japan.
M
M
Miyaki
K
K
Tanaka
R
R
Kikuchi-Yanoshita
M
M
Muraoka
M
M
Konishi
M
M
Takeichi
D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion; D002455:Cell Division; D003110:Colonic Neoplasms / Q000201:enzymology / Q000473:pathology*; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D014162:Transfection; D014407:Tumor Cells, Cultured
D015820:Cadherins; D018093:Gelatinases