Expression and prognostic relevance of PRAME in primary osteosarcoma.

The preferentially expressed antigen of melanoma (PRAME), a cancer-testis antigen with unknown function, is expressed in many human malignancies and is considered an attractive potential target for tumor immunotherapy. However, studies of its expression and function in osteosarcoma have rarely been reported. In this study, we found that PRAME is expressed in five osteosarcoma cell lines and in more than 70% of osteosarcoma patient specimens. In addition, an immunohistochemical analysis showed that high PRAME expression was associated with poor prognosis and lung metastasis. Furthermore, PRAME siRNA knockdown significantly suppressed the proliferation, colony formation, and G1 cell cycle arrest in U-2OS cells. Our results suggest that PRAME plays an important role in cell proliferation and disease progression in osteosarcoma. However, the detail mechanisms of PRAME function in osteosarcoma require further investigation.

[1]  S. Paydaş.  Is everything known in all faces of iceberg in PRAME? , 2008, Leukemia research.

[2]  E. Álava,et al.  Bone sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. , 2014, Annals of oncology : official journal of the European Society for Medical Oncology.

[3]  F. Berthold,et al.  The Tumor-Associated Antigen PRAME Is Universally Expressed in High-Stage Neuroblastoma and Associated with Poor Outcome , 2004, Clinical Cancer Research.

[4]  L. O’Driscoll,et al.  Prevalence and prognostic and predictive relevance of PRAME in breast cancer , 2008, Breast Cancer Research and Treatment.

[5]  Vedrana Milinkovic,et al.  Identification of genes associated with non-small-cell lung cancer promotion and progression. , 2010, Lung cancer.

[6]  D. Steinbach,et al.  PRAME expression is not associated with down-regulation of retinoic acid signaling in primary acute myeloid leukemia. , 2007, Cancer genetics and cytogenetics.

[7]  K. Tanriverdi,et al.  PRAME mRNA levels in cases with acute leukemia: Clinical importance and future prospects , 2005, American journal of hematology.

[8]  W. Winkelmann,et al.  Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  A. Hart,et al.  PRAME expression and clinical outcome of breast cancer , 2008, British Journal of Cancer.

[10]  S. Ferrari,et al.  Neoadjuvant chemotherapy with high-dose Ifosfamide, high-dose methotrexate, cisplatin, and doxorubicin for patients with localized osteosarcoma of the extremity: a joint study by the Italian and Scandinavian Sarcoma Groups. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  S. Carter,et al.  Latest developments in limb-salvage surgery in osteosarcoma , 2011, Expert review of anticancer therapy.

[12]  Brent L Wood,et al.  The preferentially expressed antigen in melanoma (PRAME) inhibits myeloid differentiation in normal hematopoietic and leukemic progenitor cells. , 2009, Blood.

[13]  R. Bernards,et al.  A causal role for the human tumor antigen preferentially expressed antigen of melanoma in cancer. , 2006, Cancer research.

[14]  Song Jin,et al.  Establishment and characteristics of two syngeneic human osteosarcoma cell lines from primary tumor and skip metastases , 2008, Acta Pharmacologica Sinica.

[15]  A. Simpson,et al.  PRAME is a membrane and cytoplasmic protein aberrantly expressed in chronic lymphocytic leukemia and mantle cell lymphoma. , 2006, Leukemia research.

[16]  S. Cavalheiro,et al.  PRAME gene expression profile in medulloblastoma. , 2011, Arquivos de neuro-psiquiatria.

[17]  B. Tombal,et al.  Tumor-associated antigen preferentially expressed antigen of melanoma (PRAME) induces caspase-independent cell death in vitro and reduces tumorigenicity in vivo. , 2005, Cancer research.

[18]  H. Saluz,et al.  Hypomethylation of PRAME is responsible for its aberrant overexpression in human malignancies , 2007, Genes, chromosomes & cancer.

[19]  R. Gorlick,et al.  Immune approaches to treating osteosarcoma , 2009, Cancer biology & therapy.

[20]  B. Tombal,et al.  Tumor associated antigen PRAME is a marker of favorable prognosis in childhood acute myeloid leukemia patients and modifies the expression of S100A4, Hsp 27, p21, IL-8 and IGFBP-2 in vitro and in vivo , 2008, Leukemia & lymphoma.

[21]  K. Partheen,et al.  Four potential biomarkers as prognostic factors in stage III serous ovarian adenocarcinomas , 2008, International journal of cancer.

[22]  P. McEwan,et al.  Leucine-rich repeat protein PRAME: expression, potential functions and clinical implications for leukaemia , 2010, Molecular Cancer.

[23]  B. Seliger,et al.  Heterogeneous expression of the tumor-associated antigens RAGE-1, PRAME, and glycoprotein 75 in human renal cell carcinoma: candidates for T-cell-based immunotherapies? , 1998, Cancer research.

[24]  M. Shiseki,et al.  Inhibition of PRAME expression causes cell cycle arrest and apoptosis in leukemic cells. , 2011, Leukemia research.

[25]  P. Coulie,et al.  Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor. , 1997, Immunity.

[26]  R. Bernards,et al.  The Human Tumor Antigen PRAME Is a Dominant Repressor of Retinoic Acid Receptor Signaling , 2005, Cell.

[27]  D. Lev,et al.  Cancer‐testis antigens expressed in osteosarcoma identified by gene microarray correlate with a poor patient prognosis , 2012, Cancer.

[28]  B. Ljung,et al.  The gene expression signatures of melanoma progression , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Lisa Mirabello,et al.  International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons , 2009, International journal of cancer.

[30]  Jia-guo Zhou,et al.  2‐D DIGE and MALDI‐TOF‐MS analysis of the serum proteome in human osteosarcoma , 2007, Proteomics. Clinical applications.