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Invasion and metastasis of renal cell carcinoma

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Abstract

Renal cell carcinoma (RCC) represents over 80 % of kidney cancer, and about 30 % of the patients with RCC develop metastasis after the surgery. Invasion of basement membrane (BM) and extracellular matrix (ECM) is an essential event in tumor invasion and metastasis. Matrix metalloproteinases (MMPs), which digest the main components of BM and ECM, are expressed in RCC. Heparanase, which degrades heparan sulfate proteoglycans, is predominantly expressed in high-grade RCCs with a positive correlation with pathological tumor stage and poor prognosis. Bone metastasis is common among the patients with RCC, and increased osteoclastic activity was observed at metastatic sites. Receptor activator of nuclear factor κB ligand (RANKL), which plays an important role in osteoclastogenesis, is predominantly expressed in high-grade RCC and its expression level is associated with bone metastasis and prognosis. Epithelial-mesenchymal transition (EMT), a switch of epithelial cells to sarcomatoid phenotype, is considered to be critical step during metastasis, and Snail, a major regulator of EMT, is predominantly expressed in high-grade RCC, and high Snail expression is a worse prognostic factor. Accordingly, heparanase, RANKL and Snail may be targets for the development of anti-tumor therapies for RCCs.

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Acknowledgments

This work was supported in part by Grant-in-Aid for Scientific Research (C) (No. 25460422) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT) (S.M.), Grain-in-Aid for Scientific Research (B) (No. 24390374) from MEXT (M.O.), and Grant-in-Aid for Scientific Research (A) (No. 24249022) from MEXT (Y.O.) and Third Term 10-year Strategy for Cancer Control (Y.O.) from the Foundation of Promotion of Cancer Research, and Project for Development of Innovative Research on Cancer Therapeutics (P-Direct) from MEXT (S. M., R.M, T.K. and M.O.).

Conflicts of interest

None of the authors has any conflicts of interest associated with this study.

Author information

Authors and Affiliations

  1. Division of Diagnostic Pathology, Keio University Hospital, 35 Shinanomachi, Shinjuku-ku, 160-8582, Tokyo, Japan

    Shuji Mikami

  2. Department of Urology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, 160-8582, Tokyo, Japan

    Mototsugu Oya, Ryuichi Mizuno & Takeo Kosaka

  3. Department of Human Care, Tohto College of Health Science, 4-2-11 Kamishiba, Fukaya, 366-0052, Saitama, Japan

    Ken-ichi Katsube

  4. Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, 160-8582, Tokyo, Japan

    Yasunori Okada

Authors
  1. Shuji Mikami
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  2. Mototsugu Oya
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  4. Takeo Kosaka
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  5. Ken-ichi Katsube
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Corresponding author

Correspondence to Shuji Mikami.

Additional information

This paper was shown in the symposium, “Molecular and Morphological approach of research on renal cell carcinoma”, at the Annual Meeting and Scientific Assembly of the 44th Annual Meeting of the Japanese Society for Clinical Molecular Morphology as “atypia of the renal cell carcinoma, invasion and metastasis” and was invited for submission to Medical Molecular Morphology.

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Mikami, S., Oya, M., Mizuno, R. et al. Invasion and metastasis of renal cell carcinoma. Med Mol Morphol 47, 63–67 (2014). https://doi.org/10.1007/s00795-013-0064-6

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