Clinicopathological significance and antitumor effect of MPHOSPH1 in testicular germ cell tumor

研究成果: ジャーナルへの寄稿記事

抄録

MPHOSPH1, which is one of the kinesin superfamily proteins, has been reported to play an essential role in the carcinogenesis and progression of several kinds of cancers. MPHOSPH1 has also been suggested to be involved in STAT3 phosphorylation in hepatocellular carcinoma. However, the biological behavior of MPHOSPH1 in testicular germ cell tumors (TGCTs) is unclear at present. The purposes of this study were to investigate the correlation between the expression of MPHOSPH1 and clinicopathological factors and to examine the efficacy of MPHOSPH1 target therapy in TGCTs. We investigated 75 formalin-fixed paraffin-embedded TGCT samples, containing a total of 86 germ cell tumor components, by immunohistochemistry and 12 frozen samples by Western blotting. Moreover, we carried out in vitro studies to clarify the antitumor effect of MPHOSPH1 knockdown in embryonal carcinoma cell lines, NEC8 and NEC14, using small interference RNA (siRNA). A significantly high expression of MPHOSPH1 was recognized in embryonal carcinoma and yolk sac tumor components compared to the seminoma component (p<0.001, respectively). Clinically, non-seminoma cases are known to have worse prognosis than pure-seminoma cases. Interestingly, high MPHOSPH1 expression was associated with distant metastasis (p=0.001), and thus with advanced-stage disease in this study. High expression of MPHOSPH1 interacted with high expression of phosphorylated STAT3 (p=0.01). The in vitro experiments demonstrated that MPHOSPH1 interruption by siRNA resulted in a significant reduction of cell migration, invasion, proliferation and colony formation in both embryonal carcinoma cell lines (p<0.001, respectively). In conclusion, MPHOSPH1 may be a potential treatment option for TGCTs, and its expression may be a novel biomarker of poor prognosis.

元の言語英語
ページ(範囲)4440-4448
ページ数9
ジャーナルJournal of Cancer
9
発行部数23
DOI
出版物ステータス出版済み - 1 1 2018

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Embryonal Carcinoma Stem Cells
Seminoma
RNA Interference
Embryonal Carcinoma
Endodermal Sinus Tumor
Cell Line
Kinesin
Germ Cell and Embryonal Neoplasms
Cellular Structures
Paraffin
Formaldehyde
Cell Movement
Hepatocellular Carcinoma
Carcinogenesis
Biomarkers
Western Blotting
Immunohistochemistry
Phosphorylation
Neoplasm Metastasis
Testicular Germ Cell Tumor

All Science Journal Classification (ASJC) codes

  • Oncology

これを引用

Clinicopathological significance and antitumor effect of MPHOSPH1 in testicular germ cell tumor. / Abe, Tatsuro; Kouhashi, Kenichi; Takemoto, Junkichi; Kinoshita, Fumio; Eto, Masatoshi; Oda, Yoshinao.

:: Journal of Cancer, 巻 9, 番号 23, 01.01.2018, p. 4440-4448.

研究成果: ジャーナルへの寄稿記事

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abstract = "MPHOSPH1, which is one of the kinesin superfamily proteins, has been reported to play an essential role in the carcinogenesis and progression of several kinds of cancers. MPHOSPH1 has also been suggested to be involved in STAT3 phosphorylation in hepatocellular carcinoma. However, the biological behavior of MPHOSPH1 in testicular germ cell tumors (TGCTs) is unclear at present. The purposes of this study were to investigate the correlation between the expression of MPHOSPH1 and clinicopathological factors and to examine the efficacy of MPHOSPH1 target therapy in TGCTs. We investigated 75 formalin-fixed paraffin-embedded TGCT samples, containing a total of 86 germ cell tumor components, by immunohistochemistry and 12 frozen samples by Western blotting. Moreover, we carried out in vitro studies to clarify the antitumor effect of MPHOSPH1 knockdown in embryonal carcinoma cell lines, NEC8 and NEC14, using small interference RNA (siRNA). A significantly high expression of MPHOSPH1 was recognized in embryonal carcinoma and yolk sac tumor components compared to the seminoma component (p<0.001, respectively). Clinically, non-seminoma cases are known to have worse prognosis than pure-seminoma cases. Interestingly, high MPHOSPH1 expression was associated with distant metastasis (p=0.001), and thus with advanced-stage disease in this study. High expression of MPHOSPH1 interacted with high expression of phosphorylated STAT3 (p=0.01). The in vitro experiments demonstrated that MPHOSPH1 interruption by siRNA resulted in a significant reduction of cell migration, invasion, proliferation and colony formation in both embryonal carcinoma cell lines (p<0.001, respectively). In conclusion, MPHOSPH1 may be a potential treatment option for TGCTs, and its expression may be a novel biomarker of poor prognosis.",
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AU - Eto, Masatoshi

AU - Oda, Yoshinao

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