Activation of signal transducer and activator of transcription 3 (Stat3) pathway in osteosarcoma cells and overexpression of phosphorylated-Stat3 correlates with poor prognosis.
Stat3 expression in cancer may have important prognostic and therapeutic value, but there has been no reports correlating Stat3 expression with prognosis in patients with osteosarcoma. The goal of this study is to correlate patient prognosis with the expression of Stat3 in osteosarcoma tissue and determine the effectiveness of blocking this pathway in osteosarcoma cell lines by Stat3 inhibitor, CDDO-Me. We examine the expression levels of Stat3 and pStat3 in osteosarcoma cell lines and primary tissues by Western blot analysis. We also evaluate the levels of pStat3 expression in osteosarcoma tissue microarray (TMA) by immunohistochemistry. We use clinical data to determine the impact of levels of Stat3 expression on patient prognosis. Finally, we evaluated the effect of CDDO-Me on the inhibition of activated Stat3 pathway in osteosarcoma cell lines using MTT assay and Western blot analysis. Stat3 is observed to be activated in osteosarcoma tissues as well as in cultured cell lines. Overexpression of pStat3 is associated with poor prognosis. CDDO-Me inhibits the growth of osteosarcoma cell lines and induces apoptosis as well. Our results suggest that Stat3 may be a prognostic indicator and potential therapeutic target for osteosarcoma. Blocking the pathway of Stat3 may lead to develop new therapeutic strategies against osteosarcoma.
Ryu
Keinosuke
K
Department of Orthopedic Surgery, Massachusetts General Hospital, Center for Sarcoma and Connective Tissue Oncology, 55 Fruit St. Jackson 1115, Boston, Massachusetts 02114, USA.
Choy
Edwin
E
Yang
Cao
C
Susa
Michiro
M
Hornicek
Francis J
FJ
Mankin
Henry
H
Duan
Zhenfeng
Z
D000293:Adolescent; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001859:Bone Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009828:Oleanolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D012516:Osteosarcoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D010766:Phosphorylation / Q000502:physiology; D011379:Prognosis; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D055815:Young Adult
D014408:Biomarkers, Tumor; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D009828:Oleanolic Acid; C445068:bardoxolone methyl