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Cyr61 expression in Osteosarcoma indicates poor prognosis and promotes intratibial growth and lung metastasis in mice
- Source :
- Journal of bone and mineral research : the official journal of the American Society for Bone and Min, Europe PubMed Central
- Publication Year :
- 2011
-
Abstract
- Osteosarcoma is the most frequent primary malignant bone tumor in children and adolescents with a high propensity for lung metastasis, the major cause of disease-related death. Reliable outcome-predictive markers and targets for osteosarcoma metastasissuppressing drugs are urgently needed for more effective treatment of metastasizing osteosarcoma, which has a current mean 5-year survival rate of approximately 20%. This study investigated the prognostic value and the biological relevance of the extracellular matrixassociated growth factor Cyr61 of the CCN family of secreted proteins in osteosarcoma and metastasis. The prognostic value of Cyr61 was assessed with Kaplan-Meier analyses based on Cyr61 immunostaining of a tissue microarray of osteosarcoma biopsies collected from 60 patients with local or metastatic disease. Effects of Cyr61 overexpression on intratibial tumor growth and lung metastasis of the low metastatic human SaOS-2 osteosarcoma cell line were examined in severe combined immunodeficiency (SCID) mice. Cyr61-provoked signaling was studied in vitro in nonmanipulated SaOS-2 cells. Cyr61 immunostaining of osteosarcoma tissue cores correlated significantly (p ¼ 0.02) with poor patient survival. Mice intratibially injected with Cyr61-overexpressing SaOS-2 cells showed faster tumor growth and an increase in number and outgrowth of lung metastases and consequently significantly (p ¼ 0.0018) shorter survival than mice injected with control SaOS-2 cells. Cyr61-evoked PI-3K/Akt/GSK3b signaling in SaOS-2 cells resulted in a subcellular redistribution of the cell cycle inhibitor p21 Cip1/WAF1 . Cyr61 has considerable potential as a novel marker for poor prognosis in osteosarcoma and is an attractive target for primary tumor- and metastases-suppressing drugs. 2012 American Society for Bone and Mineral Research.
- Subjects :
- Male
Oncology
Lung Neoplasms
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Mice, SCID
Metastasis
Glycogen Synthase Kinase 3
Mice
Phosphatidylinositol 3-Kinases
Cytosol
0302 clinical medicine
Cell Movement
Orthopedics and Sports Medicine
Osteosarcoma
0303 health sciences
Tissue microarray
Prognosis
Immunohistochemistry
Primary tumor
3. Good health
2712 Endocrinology, Diabetes and Metabolism
030220 oncology & carcinogenesis
CYR61
Female
10046 Balgrist University Hospital, Swiss Spinal Cord Injury Center
Signal Transduction
Cyclin-Dependent Kinase Inhibitor p21
medicine.medical_specialty
610 Medicine & health
03 medical and health sciences
2732 Orthopedics and Sports Medicine
Cell Line, Tumor
Internal medicine
10049 Institute of Pathology and Molecular Pathology
medicine
Animals
Humans
Neoplasm Invasiveness
Survival rate
030304 developmental biology
Severe combined immunodeficiency
Glycogen Synthase Kinase 3 beta
Tibia
business.industry
Growth factor
medicine.disease
Survival Analysis
10021 Department of Trauma Surgery
business
Proto-Oncogene Proteins c-akt
Cysteine-Rich Protein 61
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Journal of bone and mineral research : the official journal of the American Society for Bone and Min, Europe PubMed Central
- Accession number :
- edsair.doi.dedup.....5113ef41235fc6ff0f75d4f00f4d6dd9