Exogenous expression of H-cadherin in CHO cells regulates contact inhibition of cell growth by inducing p21 expression.

Abstract

The impact of the cadherins in human cancers is becoming better understood. However, few studies have directly tested the hypothesis that H-cadherin, a tailless cadherin, is actually a tumor suppressor, and no published studies have addressed the question of how H-cadherin suppresses cellular transformation. We report here the influence that exogenous expression of H-cadherin imposes on growth, morphology, clonogenicity and tumorigenicity of Chinese hamster ovarian (CHO) cells. H-cadherin expression in CHO cells resulted in tighter adhesion of multicellular aggregates and reduced cell proliferation. In addition to enhancement of cell-cell adhesion, exogenous H-cadherin expression also inhibited cell proliferation and the ability to form colonies in soft agar. Furthermore, expression of H-cadherin in CHO cells led to complete suppression of subcutaneous tumor growth in nude mice. Seeding the H-cadherin expressing CHO cells on culture plates coated with recombinant H-cadherin amino-terminal fragments resulted in inhibition of cell proliferation that was accompanied by increased expression of the cdk inhibitor p21. These results support the role of H-cadherin as a tumor suppressor participating in contact inhibition of cell growth, possibly by inducing p21 expression.