Adenovirus-mediated gene delivery of tissue inhibitor of metalloproteinases-3 inhibits invasion and induces apoptosis in melanoma cells

M Ahonen, AH Baker, VM Kähäri - Cancer research, 1998 - AACR
M Ahonen, AH Baker, VM Kähäri
Cancer research, 1998AACR
We have used adenovirus-mediated gene delivery of tissue inhibitor of metalloproteinase
(TIMP)-1,-2, and-3 to examine their effect on the invasion capacity of metastatic melanoma
cell lines SK-Mel-5 and A2058. Infection of melanoma cells with recombinant replication-
deficient adenoviruses coding for TIMP-1, TIMP-2, and TIMP-3 resulted in marked secretion
of TIMP-1 and TIMP-2 to culture medium and accumulation of TIMP-3 to matrix.
Overexpression of TIMP-3 inhibited invasion of SK-Mel-5 and A2058 cells through …
Abstract
We have used adenovirus-mediated gene delivery of tissue inhibitor of metalloproteinase (TIMP)-1, -2, and -3 to examine their effect on the invasion capacity of metastatic melanoma cell lines SK-Mel-5 and A2058. Infection of melanoma cells with recombinant replication-deficient adenoviruses coding for TIMP-1, TIMP-2, and TIMP-3 resulted in marked secretion of TIMP-1 and TIMP-2 to culture medium and accumulation of TIMP-3 to matrix. Overexpression of TIMP-3 inhibited invasion of SK-Mel-5 and A2058 cells through reconstituted basement membrane (Matrigel) even more potently than TIMP-1 and TIMP-2. In addition, overproduction of TIMP-3 reduced attachment of melanoma cells to type I and IV collagen and fibronectin and resulted in apoptosis in both SK-Mel-5 and A2058 cells. These results propose a novel role for TIMP-3 in regulation of invasion and survival of malignant cells and suggest potential use for TIMP-3 in adenovirus-mediated gene therapy of malignant melanoma.
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