Possible Role of Sonic Hedgehog and Epithelial-Mesenchymal Transition in Renal Cell Cancer Progression
Behnsawy Hosny M., Shigemura Katsumi, Meligy Fatma Y., Yamamichi Fukashi, Yamashita Masuo, Haung Wen-Chin, Li Xiangyan, Miyake Hideaki, Tanaka Kazushi, Kawabata Masato, Shirakawa Toshiro, Fujisawa Masato,
소속 상세정보
( Behnsawy Hosny M. )
Kobe University Graduate School of Medicine Department of Urology
( Shigemura Katsumi )
Kobe University Graduate School of Medicine Department of Urology
( Meligy Fatma Y. )
Egypt Assiut University Faculty of Medicine Department of Urology
( Yamamichi Fukashi )
Kobe University Graduate School of Medicine Department of Urology
( Yamashita Masuo )
Japan Shinko Hospital Department of Urology
( Haung Wen-Chin )
USA Cedars-Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute Department of Medicine
( Li Xiangyan )
USA Cedars-Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute Department of Medicine
( Miyake Hideaki )
Kobe University Graduate School of Medicine Department of Urology
( Tanaka Kazushi )
Kobe University Graduate School of Medicine Department of Urology
( Kawabata Masato )
Japan Kobe University Graduate School of Medicine Infectious Center
( Shirakawa Toshiro )
Kobe University Graduate School of Medicine Department of Urology
( Fujisawa Masato )
Kobe University Graduate School of Medicine Department of Urology
KMID : 0358320130540080547
Abstract
Purpose: Sonic hedgehog (Shh) signaling and epithelial-mesenchymal transition (EMT) are both known to relate to cancer progression. The purpose of this study was to investigate the role of Shh signaling and EMT in renal cell carcinoma (RCC). Materials and Methods: Cell proliferation was assayed in RCC cell lines in the presence or absence of a Shh signaling stimulator, recombinant Shh (r-Shh) protein, or a Shh signaling inhibitor, cyclopamine. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed to study the expression of EMT markers (E-cadherin, N-cadherin, and vimentin) and osteonectin. The expression of Ki-67, Gli-1, osteonectin, and EMT markers in nephrectomy specimens from RCC patients was also measured by immunohistochemical (IHC) staining. Results: RCC cells showed enhanced cell proliferation by r-Shh protein, whereas cell proliferation was suppressed by the addition of cyclopamine in RenCa cells. Real-time RT-PCR showed that r-Shh suppressed the expression of E-cadherin and that this suppression was partly blocked by cyclopamine alone in RenCa cells. In the IHC results, osteonectin significantly correlated with vein sinus invasion (p=0.0218), and the expression of vimentin significantly correlated with lymphatic invasion (p=0.0392). Conclusions: Shh signaling and EMT play roles in RCC progression, and the Shh signaling inhibitor cyclopamine might be a possible molecular targeted therapeutic strategy for RCC.
키워드
Epithelial-mesenchymal transition; Hedgehogs; Renal cell carcinoma
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