title: Endometrial cancer invasion depends on cancer-derived tumor necrosis factor-alpha and stromal derived hepatocyte growth factor.
abstract: Cancer invasion is an outcome of interactions of the cancer and the host cell. It is now becoming increasingly clear that ovarian hormones have a huge influence on such intercommunications in various types of cancers. 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, i.e., estrogen stimulates tumor necrosis factor-alpha expression from the endometrial cancer cells, which, in turn, induces the stromal expression of hepatocyte growth factor (HGF), conferring the enhanced NK4 (HGF-antagonist/angiogenesis inhibitor)-sensitive 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 alpha(v)beta(5) 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.
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Dong Soon
authors.initials: DS
authors.lastname: Choi
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jong-Hyuck
authors.initials: JH
authors.lastname: Yoon
authors.forename: Seung-Chul
authors.initials: SC
authors.lastname: Yoo
authors.forename: Hantae
authors.initials: H
authors.lastname: Jo
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Lee
authors.forename: Churl K
authors.initials: CK
authors.lastname: Min
authors.forename: Hee-Sug
authors.initials: HS
authors.lastname: Ryu
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000473:pathology*; D004967:Estrogens / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D009361:Neoplasm Invasiveness; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000032:analysis; D017154:Stromal Cells / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D004967:Estrogens; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019030:Receptors, Vitronectin; D014409:Tumor Necrosis Factor-alpha; C064660:integrin alphaVbeta5; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases