Increased RANKL expression is related to tumour migration and metastasis of renal cell carcinomas

Shuji Mikami, Ken Ichi Katsube, Mototsugu Oya, Masaru Ishida, Takeo Kosaka, Ryuichi Mizuno, Satsuki Mochizuki, Tohru Ikeda, Makio Mukai, Yasunori Okada

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Receptor activator of NF-κB ligand (RANKL) and its receptor, receptor activator of NF-κB (RANK), play a key role in osteoclastogenesis, and osteoprotegerin (OPG) acts as a decoy receptor for RANKL. We investigated the role of the RANKL-RANK-OPG system in renal cell carcinomas (RCCs), which frequently metastasize to bones. Real-time quantitative PCR revealed that RANKL mRNA expression was higher in clear cell RCCs than in papillary and chromophobe RCCs. Similarly, RANKL protein expression level in clear cell RCCs was higher than that in papillary and chromophobe RCCs, showing positive correlations with the primary tumour stage and distant metastasis. There was no significant association between the expression level of RANK, OPG and histological subtypes of RCC. RANKL and RANK expression was observed in metastatic RCCs in the bone and other organs, suggesting that they play a role in metastasis to the bone and other organs. Recombinant RANKL protein stimulated migration of a clear cell RCC cell line, Caki-1, in vitro, and this enhanced migration was inhibited by the administration of recombinant OPG protein. Furthermore, multivariate Cox analysis revealed that elevated RANKL and RANK expression with low-OPG expression was a significant and independent predictor of recurrence, bone metastasis and a poor prognosis. These data suggest that the RANKL-RANK-OPG system is involved not only in the bone metastasis of RCCs but also in metastasis to other organs through the stimulation of cancer cell migration.

Original languageEnglish
Pages (from-to)530-539
Number of pages10
JournalJournal of Pathology
Volume218
Issue number4
DOIs
Publication statusPublished - 2009 Aug

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Renal Cell Carcinoma
Osteoprotegerin
Neoplasm Metastasis
Neoplasms
Bone and Bones
RANK Ligand
Recombinant Proteins
Osteogenesis
Cell Movement
Real-Time Polymerase Chain Reaction
Multivariate Analysis
Ligands
Recurrence
Cell Line
Messenger RNA

Keywords

  • Bone metastasis
  • Migration
  • OPG
  • Prognosis
  • RANK
  • RANKL
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Increased RANKL expression is related to tumour migration and metastasis of renal cell carcinomas. / Mikami, Shuji; Katsube, Ken Ichi; Oya, Mototsugu; Ishida, Masaru; Kosaka, Takeo; Mizuno, Ryuichi; Mochizuki, Satsuki; Ikeda, Tohru; Mukai, Makio; Okada, Yasunori.

In: Journal of Pathology, Vol. 218, No. 4, 08.2009, p. 530-539.

Research output: Contribution to journalArticle

Mikami, Shuji ; Katsube, Ken Ichi ; Oya, Mototsugu ; Ishida, Masaru ; Kosaka, Takeo ; Mizuno, Ryuichi ; Mochizuki, Satsuki ; Ikeda, Tohru ; Mukai, Makio ; Okada, Yasunori. / Increased RANKL expression is related to tumour migration and metastasis of renal cell carcinomas. In: Journal of Pathology. 2009 ; Vol. 218, No. 4. pp. 530-539.
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AU - Kosaka, Takeo

AU - Mizuno, Ryuichi

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