title: Invasion and metastasis of renal cell carcinoma.
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.
authors.affiliation: Division of Diagnostic Pathology, Keio University Hospital, 35 Shinanomachi, Shinjuku-ku, 160-8582, Tokyo, Japan, mikami@a7.keio.jp.
authors.forename: Shuji
authors.initials: S
authors.lastname: Mikami
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Oya
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Mizuno
authors.forename: Takeo
authors.initials: T
authors.lastname: Kosaka
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Katsube
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Okada
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000503:physiopathology*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D053245:RANK Ligand / Q000378:metabolism; D000099175:Heparanase
chemical_list: D014408:Biomarkers, Tumor; D005966:Glucuronidase; D020782:Matrix Metalloproteinases; D053245:RANK Ligand; D000099175:Heparanase; C505688:TNFSF11 protein, human