title: Hepatoma derived growth factor (HDGF) dynamics in ovarian cancer cells.
abstract: As a leading cause of cancer death among women, identification of pathophysiologically-relevant biomarkers for ovarian cancer is important. The heparin binding, hepatoma-derived growth factor (HDGF) is overexpressed in ovarian cancer cell lines and may have prognostic value, but the mechanism by which this predominantly nuclear protein is secreted or functions is unknown. In this study, we focused on the circumstances under which HDGF is released by cells and the functional relevance of extracellular HDGF in the context of ovarian cancer. Immunofluorescence imaging showed nuclear localization of HDGF in ovarian cells, but unlike what is reported for other cell types, HDGF was minimally secreted into the media. However, HDGF was passively released by necrotic and late apoptotic cells. Extracellular HDGF was functionally relevant as it stimulated phosphorylation of ERK 1/2 and P38 in both non-cancer and ovarian cancer cells, and enhanced cellular migration. Overall, our study uncovers a novel function of HDGF as a messenger of cellular condition (alarmin) which in-turn modulates cellular function-aspects that could be used as a biomarker for ovarian cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA.
authors.forename: Karuna
authors.initials: K
authors.lastname: Giri
authors.affiliation: Department of Anesthesiology, Mayo Clinic, 4-184 W Jos SMH, 200 1st St SW, Rochester, MN, 55905, USA.|Department of Physiology and Biomedical Engineering, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Pabelick
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, 1100 N Lindsay Ave, Oklahoma City, OK, 73104, USA.
authors.forename: Priyabrata
authors.initials: P
authors.lastname: Mukherjee
authors.affiliation: Department of Anesthesiology, Mayo Clinic, 4-184 W Jos SMH, 200 1st St SW, Rochester, MN, 55905, USA. Prakash.ys@mayo.edu.|Department of Physiology and Biomedical Engineering, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA. Prakash.ys@mayo.edu.
authors.forename: Y S
authors.initials: YS
authors.lastname: Prakash
mesh_terms: D000067531:Alarmins / Q000378:metabolism; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D011379:Prognosis
chemical_list: C575685:AIMP2 protein, human; D000067531:Alarmins; D014408:Biomarkers, Tumor; D036341:Intercellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C051610:hepatoma-derived growth factor; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Alarmin; Cell death; Migration; Tumor signaling