Versican promotes tumor progression, metastasis and predicts poor prognosis in renal carcinoma

Yozo Mitsui, Hiroaki Shiina, Taku Kato, Shigekatsu Maekawa, Yutaka Hashimoto, Marisa Shiina, Mitsuho Imai-Sumida, Priyanka Kulkarni, Pritha Dasgupta, Ryan Kenji Wong, Miho Hiraki, Naoko Arichi, Shinichiro Fukuhara, Soichiro Yamamura, Shahana Majid, Sharanjot Saini, Guoren Deng, Rajvir Dahiya, Koichi Nakajima, Yuichiro Tanaka

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

The proteoglycan versican (VCAN) promotes tumor progression and enhances metastasis in several cancers; however, its role in clear cell renal cell carcinoma (ccRCC) remains unknown. Recent evidence suggests that VCAN is an important target of chromosomal 5q gain, one of the most prevalent genetic abnormalities in ccRCC. Thus, we investigated whether VCAN expression is associated with the pathogenesis of ccRCC. VCAN expression was analyzed using three RCC and normal kidney cell lines as well as a clinical cohort of 84 matched ccRCC and normal renal tissues. Functional analyses on growth and progression properties were performed using VCAN-depleted ccRCC cells. Microarray expression profiling was employed to investigate the target genes and biologic pathways involved in VCAN-mediated ccRCC carcinogenesis. ccRCC had elevated VCAN expression in comparison with normal kidney in both cell lines and clinical specimens. The elevated expression of VCAN was significantly correlated with metastasis (P < 0.001) and worse 5-year overall survival after radical nephrectomy (P - 0.014). In vitro, VCAN knockdown significantly decreased cell proliferation and increased apoptosis in Caki-2 and 786-O cells, and this was associated with alteration of several TNF signaling-related genes such as TNFa, BID, and BAK. Furthermore, VCAN depletion markedly decreased cell migration and invasion which correlated with reduction of MMP7 and CXCR4. These results demonstrate that VCAN promotes ccRCC tumorigenesis and metastasis and thus is an attractive target for novel diagnostic, prognostic, and therapeutic strategies.

Original languageEnglish (US)
Pages (from-to)884-895
Number of pages12
JournalMolecular Cancer Research
Volume15
Issue number7
DOIs
Publication statusPublished - Jul 2017
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

Cite this

Mitsui, Y., Shiina, H., Kato, T., Maekawa, S., Hashimoto, Y., Shiina, M., ... Tanaka, Y. (2017). Versican promotes tumor progression, metastasis and predicts poor prognosis in renal carcinoma. Molecular Cancer Research, 15(7), 884-895. https://doi.org/10.1158/1541-7786.MCR-16-0444