Tumor Cell Invasion Inhibited by TIMP-2

来自 EBSCO

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作者：

A Adriana，M Antonella，S Leonardo，LA Liotta，PD Brown，WG Stetler-Stevenson

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摘要：

The 72-kd type IV collagenase is a member of the collagenase enzyme family that has been closely linked with the invasive phenotype of cells. Previous studies have shown that both normal cells and highly invasive cells produce the 72-kd type IV procollagenase enzyme in a complexed form consisting of the proenzyme and a novel , . The balance between activated enzyme and available inhibitor is thought to be a critical determinant of the matrix proteolysis associated with a variety of pathologic processes, including cell invasion. In the present study, we demonstrate that alteration of the metalloproteinase-balance in favor of excess inhibitor blocks cell invasion of a reconstituted . The cell line produces both the 72-kd and the 92-kd type IV collagenases. Alteration of the type IV balance was achieved by addition of free or antibodies to 72-kd type IV collagenase. Native, purified was inhibitory in the range of 1-25 micrograms/mL. Addition of specific antiserum against the 72-kd type IV collagenase, which did not cross-react with the 92-kd type IV collagenase, inhibited cell invasion to the same extent. These results suggest that metalloproteinases, in particular the 72-kd type IV collagenase, are critical for cell invasion of the reconstituted . Our findings demonstrate that addition of the endogenous inhibitor is able to block invasion. Thus, we recommend initiation of in vivo studies of the therapeutic potential of to block cell invasion and intravasation into the .

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关键词：

Tumor Cells, Cultured Animals Humans Mice Neoplasm Invasiveness Metalloendopeptidases Microbial Collagenase Neoplasm Proteins Tissue Inhibitor of Metalloproteinase-2 Antineoplastic Agents