Tumorigenesis and prognostic role of hepatoma-derived growth factor in human gliomas.
Hepatoma-derived growth factor (HDGF) is a neurotrophic factor found in mouse spinal cord and hippocampal neurons. In various malignant tumors, the role of HDGF in tumor progression and its use as a diagnostic biomarker or therapeutic target have been extensively explored. However, the prognostic function and mitogenic role of HDGF in gliomagenesis are yet to be verified. In this study, we found a significant incidence of HDGF prevalence between the different pathological types and stages of glioma in 105 patients. We also found a prognostic significance in 41 glioblastoma multiforme (GBM) patients, with prevalence of nuclear HDGF predicting short survival of patients with GBM after surgery. To delineate the mitogenic role of HDGF in gliomagenesis, an adenoviral-expressed HDGF small interfering RNA (Ad-HDGF siRNA) was used to knock down expression of nuclear HDGF. After knocking down nuclear HDGF expression in human GBM cells, cell growth and cell invasion and induction on apoptosis by caspase-3 activation were significantly inhibited. We conclude that HDGF is a mitogenic growth factor in glioma progression and can be a useful prognostic marker for GBM and therapeutic target for clinical management of glioma in the future.
Division of Neurosurgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC.
Shu-Shong
SS
Hsu
Chih-Hao
CH
Chen
Guei-Sheung
GS
Liu
Ming-Hong
MH
Tai
Jyh-Seng
JS
Wang
Jain-Ching
JC
Wu
Mei-Lang
ML
Kung
Elsa C
EC
Chan
Li-Feng
LF
Liu
D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002448:Cell Adhesion; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D018450:Disease Progression; D004338:Drug Combinations; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005910:Glioma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D004338:Drug Combinations; D036341:Intercellular Signaling Peptides and Proteins; D007797:Laminin; D011509:Proteoglycans; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C051610:hepatoma-derived growth factor; C059485:matrigel; D003094:Collagen; D053148:Caspase 3