2009
DOI: 10.1002/path.2567
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Increased RANKL expression is related to tumour migration and metastasis of renal cell carcinomas

Abstract: Receptor activator of NF-kappaB ligand (RANKL) and its receptor, receptor activator of NF-kappaB (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… Show more

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Cited by 92 publications
(89 citation statements)
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“…RANKL interacts with RANK and, in turn, recruits tumor necrosis factor receptor-associated factors (TRAFs) (27), leading to the activation of NF-κB, c-Jun N-terminal kinase (JNK), p38, ERK and Akt (28)(29)(30). Recent studies (4,(12)(13)(14)(15) have shown that RANK is also expressed on the surface of certain cancer cells and that RANKL functions as a chemokine and directs RANK-expressing cancer cells to preferentially migrate into bone, which is the crucial and initial step for bone metastasis. However, the manner in which this cytokine is involved in tumor metastasis remains to be elucidated.…”
Section: Discussionmentioning
confidence: 99%
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“…RANKL interacts with RANK and, in turn, recruits tumor necrosis factor receptor-associated factors (TRAFs) (27), leading to the activation of NF-κB, c-Jun N-terminal kinase (JNK), p38, ERK and Akt (28)(29)(30). Recent studies (4,(12)(13)(14)(15) have shown that RANK is also expressed on the surface of certain cancer cells and that RANKL functions as a chemokine and directs RANK-expressing cancer cells to preferentially migrate into bone, which is the crucial and initial step for bone metastasis. However, the manner in which this cytokine is involved in tumor metastasis remains to be elucidated.…”
Section: Discussionmentioning
confidence: 99%
“…A number of studies have examined and confirmed the link between the RANK/RANKL pathway and propensity to metastasize to the bone (4,12,31). Recently, clinical trials with a fully human anti-RANKL antibody, denosumab, have been initiated in patients with prostate and breast cancer bone metastases with promising results (32,33).…”
Section: A B Cmentioning
confidence: 99%
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“…Interestingly, recent studies found that functional RANK was expressed in some primary and some secondary bone tumors, including osteosarcoma (5,6), chondrosarcoma (7), breast cancer (8), prostate cancer (9,10), renal cell cancer (11) and malignant melanoma (8). RANKL can promote cancer cell migration and invasion in in vitro experiments, and induce osteoclast chemotaxis (7,10,12).…”
Section: Introductionmentioning
confidence: 99%
“…Сигнальный путь RANK / RANKL / OPG достаточно изучен в доклинических исследованиях, выработанная гипотеза об участии этих маркеров в образовании мета-стазов в костной ткани сподвигла ученых к их изучению в естественных условиях [19][20][21]. В клинических условиях нескольких исследований обнаружили связь между высо-ким уровнем RANK в первичной опухоли и склонностью к развитию костных метастазов [7,22].…”
Section: Discussionunclassified