H-CADHERIN EXPRESSION INHIBITS IN-VITRO INVASIVENESS AND TUMOR-FORMATION IN-VIVO

H-cadherin is a newly characterized cadherin molecule whose expression is decreased in a variety of human carcinoma cells, suggesting that i t may play a role in maintaining normal cellular phenotype, To investi gate how re-expression of H-cadherin could influence the malignant phe notype of human breast carcinoma cells in vivo, we transfected both co ntrol and H-cadherin expression vectors into human breast cancer cells (MDAMB435), which do not express H-cadherin constitutively. We found that invasiveness of these cells could be prevented by transfection wi th H-cadherin, We also compared the ability of control- and H-cadherin -transfected cells to induce subcutaneous tumors after injection into mammary fat pads of nude mice. Our results show that H-cadherin transf ection produced a marked inhibition of tumor growth and modified the m orphology of tumor cells: tumors from mice injected with control cells were significantly larger and contained larger cells having a higher degree of pleomorphism than those of tumors generated from carcinoma c ells expressing H-cadherin, Altogether, these results indicate that H- cadherin expression antagonizes tumor growth in nude mice, presumably by enhancing cell-cell association in a tissue environment. These find ings strongly suggest that H-cadherin could provide a possible target for corrective gene therapy against breast cancer.