Stress-induced phosphoprotein 1 as a secreted biomarker for human ovarian cancer promotes cancer cell proliferation.
Ovarian cancers are frequently not diagnosed until advanced stages, resulting in a high case fatality rate. Because of this, more tumor markers, in addition to CA125, for detecting and monitoring ovarian cancer are needed. During a systematic search for potential biomarkers of ovarian cancer, we compared the protein profiles between tumor interstitial fluid and normal interstitial fluid of ovaries, rationalizing that abnormal levels of proteins in tumor interstitial fluid may be detected in peripheral blood and thus serve as easily accessible tumor markers. Here, we show that stress-induced phosphoprotein 1 (STIP1) was secreted by ovarian cancer tissues into the peripheral blood of patients, resulting in a significant increase of serum levels of STIP1 in cancer patients compared with those in age-matched normal controls. Our results further indicated that combined use of CA125 and STIP1 may increase early detection of ovarian cancer. Functionally, recombinant STIP1 significantly induced ERK phosphorylation, promoted DNA synthesis, and increased Ki-67 immunoreactivity in ovarian cancer cells, suggesting that STIP1 in vitro promotes cell proliferation. Colocalization of STIP1 and phospho-ERK in human ovarian cancer tissues also supports an in vivo activation of ERK by STIP1. Further understanding of molecular roles of STIP1 in human ovarian cancer may shed light on its pathophysiology and development of novel therapeutic strategies.
Wang
Tzu-Hao
TH
Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Tao-Yuan, Taiwan. knoxtn@cgmh.org.tw
Chao
Angel
A
Tsai
Chia-Lung
CL
Chang
Chih-Long
CL
Chen
Shun-Hua
SH
Lee
Yun-Shien
YS
Chen
Jen-Kun
JK
Lin
Yi-Jun
YJ
Chang
Pi-Yueh
PY
Wang
Chin-Jung
CJ
Chao
An-Shine
AS
Chang
Shuenn-Dyh
SD
Chang
Ting-Chang
TC
Lai
Chyong-Huey
CH
Wang
Hsin-Shih
HS
D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000097:blood*; D015153:Blotting, Western; D018394:CA-125 Antigen / Q000097:blood; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017931:DNA Primers; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006360:Heat-Shock Proteins / Q000097:blood*; D006801:Humans; D007150:Immunohistochemistry; D010051:Ovarian Neoplasms / Q000097:blood* / Q000473:pathology
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D017931:DNA Primers; D006360:Heat-Shock Proteins; C079373:STIP1 protein, human