Increased production and secretion of HGF α‐chain and an antagonistic HGF fragment in a human breast cancer progression model

摘要: Invasive human breast carcinomas frequently coexpress increased hepatocyte growth factor (HGF) and its receptor Met, suggesting that establishment of an autocrine HGF loop is important in malignant disease. This study examines the expression patterns Met activation during tumorigenesis metastasis using a MCF10A-based model Ha-Ras-induced cancer progression. Deregulation cadherin-based cell-cell adhesions, decreased cytokeratins 8/18 activity matrix metalloproteinases such as MMP-2 occurs premalignant (metastatic) cell lines compared to parental nonmalignant line. Compared benign parent line, exhibit secretion full length α-chain elevated tyrosine phosphorylation complete medium. Interestingly, cells also secrete ∼55 kDa fragment. Epitope mapping fragment supports presence N-terminal domain with truncation C-terminal domain. The shows mobility SDS-PAGE faster than α-chain, but slightly slower NK4, previously established antagonist HGF. separated binds animmobilized Met-IgG fusion protein, inhibits both HGF/Met-IgG binding HGF-induced Met-tyrosine phosphorylation. These results are first demonstration antagonistic secreted carcinoma progression, which may have negative regulatory effect on signaling epithelial cells. © 2009 UICC