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 it may play a role in maintaining normal cellular phenotype. To investigate how re-expression of H-cadherin could influence the malignant phenotype of human breast carcinoma cells in vivo, we transfected both control 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 with 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 transfection produced a marked inhibition of tumor growth and modified the morphology 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 cells 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 findings strongly suggest that H-cadherin could provide a possible target for corrective gene therapy against breast cancer.
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School and Harvard Institutes of Medicine, Boston, MA 02115, USA. slee2@bidmc.harvard.edu
S W
SW
Lee
C L
CL
Reimer
D B
DB
Campbell
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P
Cheresh
R B
RB
Duda
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O
Kocher
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D015820:Cadherins / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics*; D014407:Tumor Cells, Cultured
D015820:Cadherins; C099972:H-cadherin