title: Suppression of prostate cancer invasive potential and matrix metalloproteinase activity by E-cadherin transfection.
abstract: Our previous studies have demonstrated the heterogeneous expression of E-cadherin in a Dunning rat prostate tumor model. From this model, cloned E-cadherin-negative cells exhibited enhanced invasive and metastatic potential when compared with E-cadherin-positive cells. In this report, we examined the invasion suppressor function of E-cadherin in these prostate tumor cell clones. The E-cadherin gene was stably transfected into E-cadherin-negative Dunning clones. E-cadherin transfection resulted in the up-regulation of the three major catenins (alpha-, beta-, and gamma-catenin) and enhanced Ca2+-dependent cellular cohesiveness. Morphological analyses of E-cadherin transfectants revealed a reversion from a fibroblastic, motile phenotype to a more stationary epithelial phenotype. Matrix metalloproteinase 2, an important marker associated with invasive and metastatic potential, was reduced in all six stable transfected lines. A concomitant decrease in cellular invasiveness was observed, as assessed in vitro by the ability of the transfected cells to invade biological matrices. These results lend further support to the hypothesis that in this experimental system, E-cadherin plays a central role in reducing the cellular invasiveness of prostatic adenocarcinoma, due in part to the down-regulation of matrix metalloproteinase 2 activity. Moreover, the data shed additional light on the possible mechanisms involved in E-cadherin-dependent modulation of invasion.
authors.affiliation: Department of Anatomy and Cell Biology, The University of Iowa, College of Medicine and The University of Iowa Cancer Center, Iowa City 52242-1109, USA.
authors.forename: J
authors.initials: J
authors.lastname: Luo
authors.forename: D M
authors.initials: DM
authors.lastname: Lubaroff
authors.forename: M J
authors.initials: MJ
authors.lastname: Hendrix
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology*; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000502:physiology*; D004790:Enzyme Induction; D018093:Gelatinases / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D015820:Cadherins; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2