Apoptotic genes as potential markers of metastatic phenotype in human osteosarcoma cell lines

• Published in: International journal of oncology Vol. 32; no. 1; pp. 17 - 31
• Main Authors: ZUCCHINI, Cinzia, ROCCHI, Anna, MANARA, Maria Cristina, DE SANCTIS, Paola, CAPANNI, Cristina, BIANCHINI, Michele, CARINCI, Paolo, SCOTLANDI, Katia, VALVASSORI, Luisa
• Format: Journal Article
• Language: English
• Published: Athens Editorial Academy of the International Journal of Oncology 2008
• Subjects: Apoptosis; Biological and medical sciences; Biomarkers, Tumor; Bone Neoplasms - genetics; Bone Neoplasms - pathology; Bone Neoplasms - secondary; Cell Cycle Proteins - genetics; Cell Line, Tumor; Cyclin D1 - genetics; Diseases of the osteoarticular system; Gene Expression Profiling; Humans; Medical sciences; NF-kappa B - genetics; NF-kappa B - physiology; Nuclear Proteins - genetics; Osteosarcoma - genetics; Osteosarcoma - pathology; Osteosarcoma - secondary; Phenotype; Signal Transduction; Tumors; Tumors of striated muscle and skeleton; Human; Genetic marker; Sarcoma; Diseases of the osteoarticular system; Malignant tumor; Metastasis; Gene expression profile; Osteoarticular system; nuclear factor-κB; U2-OS; metastases; Phenotype; microarray; Cancerology; Osteosarcoma; Established cell line; Advanced stage; Transcription factor NFκB; Bone; Cancer; Apoptosis
• DOI: 10.3892/ijo.32.1.17
• ISSN: 1019-6439

Metastasis is the most frequent cause of death among patients with osteosarcoma. We have previously demonstrated in independent experiments that the forced expression of L/B/K ALP and CD99 in U-2 OS osteosarcoma cell lines markedly reduces the metastatic ability of these cancer cells. This behavior makes these cell lines a useful model to assess the intersection of multiple and independent gene expression signatures concerning the biological problem of dissemination. With the aim to characterize a common transcriptional profile reflecting the essential features of metastatic behavior, we employed cDNA microarrays to compare the gene expression profiles of L/B/K ALP- and CD99-transfected osteosarcoma clones showing low metastatic ability with those of osteosarcoma cell lines showing contrasting behavior. Changes in gene expression were validated by real-time PCR and immunohistochemistry in independent samples. In our study we identified several differentially expressed genes (GADD45alpha, VCP, DHX9, survivin, alpha-catulin, ARPC1B) related to growth arrest and apoptosis. Most of these genes are functionally related with the nuclear factor (NF)-kappaB cell survival pathway that appeared to be inhibited in the less malignant osteosarcoma cells. Hence, we propose the inhibition of the NF-kappaB pathway as a rational strategy for effective management of human osteosarcoma.