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RANK-Fc inhibits malignancy via inhibiting ERK activation and evoking caspase-3-mediated anoikis in human osteosarcoma cells

Akiyama, Toru and Choong, Peter F. M and Dass, Crispin R (2010) RANK-Fc inhibits malignancy via inhibiting ERK activation and evoking caspase-3-mediated anoikis in human osteosarcoma cells. Clinical and Experimental Metastasis, 27 (4). pp. 207-215. ISSN 0262-0898

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Abstract

Osteosarcoma (OS) is the most common primary malignant bone tumour, mainly afflicting the young. While there has been substantial improvement in treatment of OS with surgery and chemotherapy in the past two decades, this disease remains a significant health problem, warranting efforts to find better therapeutic options. In this study, we examined the RANK/RANKL axis in OS cells, using a RANK-Fc protein to perturb this coupling in an effort to reduce OS cell growth. RANK-Fc suppressed OS cell migration (P\0.005), invasion ability (P\0.05), and anchorage-independent ability in collagen- 1 gel (P\0.005) following induction of anoikis and activation of caspase-3. OS cell proliferation was not perturbed by RANK-Fc. The anti-invasion and anti-metastasis capability of RANK-Fc is attributed to reduced extracellular signal-regulated protein kinase (ERK) signaling via RANKFc, though activation of NFjB, and altered expression of Akt, p38, JNK, and matrix metalloproteinase (MMP)-2 and -9 were ruled out. In vivo, activity of the RANK-Fc against OS cell migration and invasion was confirmed in a model strictly monitoring metastasis. Thus, RANK-Fc, given its ability to directly reduce OS aggression, is a potential drug candidate.

Item Type: Article
Uncontrolled Keywords: ResPubID21864. osteosarcoma, ERK, RANK, RANKL, tumours, metastasis, anoikis, bone cancer
Subjects: Faculty/School/Research Centre/Department > School of Biomedical and Health Sciences
FOR Classification > 0304 Medicinal and Bimolecular Chemistry
FOR Classification > 1112 Oncology and Carcinogenesis
SEO Classification > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions)
Depositing User: VUIR
Date Deposited: 04 Nov 2011 00:47
Last Modified: 23 Jan 2015 02:48
URI: http://vuir.vu.edu.au/id/eprint/7569
DOI: 10.1007/s10585-010-9319-y
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Citations in Scopus: 11 - View on Scopus

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