title: Hepatocyte growth factor-like protein is required for prostate tumor growth in the TRAMP mouse model.
abstract: The Ron receptor is deregulated in a variety of cancers. Hepatocyte growth factor-like protein (HGFL) is the ligand for Ron and is constitutively secreted from hepatocytes into the circulation. While a few recent reports have emerged analyzing ectopic HGFL overexpression of in cancer cells, no studies have examined host-produced HGFL in tumorigenesis. To examine HGFL function in prostate cancer, the TRAMP mouse model, which is predisposed to develop prostate tumors, was utilized. Prostate tumors from TRAMP mice exhibit elevated levels of HGFL, which correlated with upregulation in human prostate cancer. To directly implicate HGFL in prostate tumorigenesis, TRAMP mice deficient in HGFL (HGFL-/-TRAMP+) were generated. HGFL-/- TRAMP+ mice developed significantly smaller prostate tumors compared to controls. Analysis of HGFL-/- tumors revealed reduced tumor vascularization. No differences in cancer cell proliferation were detected between HGFL-/- TRAMP+ and HGFL+/+ TRAMP+ mice. However, a significant increase in cancer cell death was detected in HGFL-/- TRAMP+ prostates which correlated with decreased pro-survival targets. In vitro analysis demonstrated robust STAT3 activation resulting in Bcl2-dependent survival following treatment of prostate cancer cells with HGFL. These data document a novel function for endogenous HGFL in prostate cancer by imparting a critical survival signal to tumor cells.
authors: Departments of Cancer Biology , Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio.
authors: Juozas
authors: J
authors: Vasiliauskas
authors: Departments of Cancer Biology , Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio.
authors: Madison A
authors: MA
authors: Nashu
authors: Department of Surgery, University of Cincinnati College of Medicine, Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio.
authors: Peterson
authors: P
authors: Pathrose
authors: Department of Surgery, University of Cincinnati College of Medicine, Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio.
authors: Sandra L
authors: SL
authors: Starnes
authors: Departments of Cancer Biology , Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio. Research Service, Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio.
authors: Susan E
authors: SE
authors: Waltz
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D017228:Hepatocyte Growth Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D011518:Proto-Oncogene Proteins; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor