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Estrogen is known to aggravate the aggressiveness of the endometrial cancer whereas progesterone seems to act as a negative factor. Insight into the mode of ovarian hormonal actions could come from the studies of its regulation of the paracrine interactions between the endometrial cancer and the normal stromal cells during the cancer invasion. In this context, we report here that estrogen promotes the endometrial cancer invasion by inducing humoral interactions between the cancer and the stromal cells, <jats:italic>i.e<\/jats:italic>., estrogen stimulates tumor necrosis factor\u2010\u03b1 expression from the endometrial cancer cells, which, in turn, induces the stromal expression of hepatocyte growth factor (HGF), conferring the enhanced NK4 (HGF\u2010antagonist\/angiogenesis inhibitor)\u2010sensitive invasion characteristic of the endometrial cancer cells. Additionally, we demonstrate a close correlation of the invasion of endometrial cancer cells with the expression and dimerization of integrin \u03b1<jats:sub>v<\/jats:sub>\u03b2<jats:sub>5<\/jats:sub> as well as the activation of focal adhesion kinase as the consequences of paracrine interactions. Thus, understanding of paracrine interactions of cancer cells with host stromal cells can yield new insight into the architecture and function of cancer invasion and metastasis, leading to a development of a new cancer therapeutic intervention. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.24238","type":"journal-article","created":{"date-parts":[[2008,12,23]],"date-time":"2008-12-23T16:04:11Z","timestamp":1230048251000},"page":"2528-2538","source":"Crossref","is-referenced-by-count":26,"title":["Endometrial cancer invasion depends on cancer\u2010derived tumor necrosis factor\u2010\u03b1 and stromal derived hepatocyte growth factor"],"prefix":"10.1002","volume":"124","author":[{"given":"Dong 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