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

Content Provider	Springer Nature Link
Author	Akiyama, Toru Choong, Peter F. M. Dass, Crispin R.
Copyright Year	2010
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 RANK-Fc, though activation of NFκB, 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.
Starting Page	207
Ending Page	215
Page Count	9
File Format	PDF
ISSN	02620898
Journal	Clinical & Experimental Metastasis
Volume Number	27
Issue Number	4
e-ISSN	15737276
Language	English
Publisher	Springer Netherlands
Publisher Date	2010-04-11
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	ERK RANK RANKL Tumour Metastasis Anoikis Surgical Oncology Hematology Oncology Biomedicine general Cancer Research
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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