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[摘要]：Laminin gamma 2 chain is a subunit of the heterotrimeric basement membrane protein laminin-332 (alpha 3 beta 3 gamma 2). The gamma 2 chain is highly expressed by hum-an cancers at the invasion fronts and this expression correlates with poor prognosis of the cancers. Our previous study showed that the gamma 2 chain s expressed as a monomer form in invading carcinoma cells. However, the role of the gamma 2 protein in tumor invasion remains unknown. Here, we demonstrate that the monomeric gamma 2 chain promotes invasive growth of human.cancer cells in vivo. First, we analyzed regulatory factors for the gamma 2 chain expression using 2 gastric carcinoma cell lines. It was found that tumor necrosis factor-alpha, by itself or in a combination with transforming growth factor-beta 1, strongly induced the secretion of the monomeric gamma 2 chain. In addition, epidermal growth factor families appeared to function as the gamma 2 chain inducers in human cancers. Next, we established T-24 bladder carcinoma cell lines expressing the full-length or the short arm of the laminin gamma 2 chain. When these cell lines were i.p. injected into nu-de mice, they produced larger tumors in the abdominal cavity and showed much stronger invasive growth onto the diaphragms than the control cell line. The gamma 2-expreSsing T-24 cells often produced ascites fluid, but scarcely the control cells. In culture, the gamma 2-expressing cells migrated through Matrigel more efficiently than the control cells. These findings imply that the gamma 2 monomer is induced in human cancers by inflammatory and stromal cytokines and promotes their invasive growth in vivo. |
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