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.

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