TY - JOUR
T1 - Hepatoma derived growth factor (HDGF) dynamics in ovarian cancer cells
AU - Giri, Karuna
AU - Pabelick, Christina M.
AU - Mukherjee, Priyabrata
AU - Prakash, Y. S.
N1 - Funding Information:
Supported by the Department of Anesthesiology, Mayo Clinic and CA136494 (PM).
Publisher Copyright:
© 2015 Springer Science+Business Media New York.
PY - 2016/3
Y1 - 2016/3
N2 - 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.
AB - 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.
KW - Alarmin
KW - Cell death
KW - Migration
KW - Tumor signaling
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U2 - 10.1007/s10495-015-1200-7
DO - 10.1007/s10495-015-1200-7
M3 - Article
C2 - 26612514
AN - SCOPUS:84957426587
SN - 1360-8185
VL - 21
SP - 329
EP - 339
JO - Apoptosis : an international journal on programmed cell death
JF - Apoptosis : an international journal on programmed cell death
IS - 3
ER -