The metastatic behavior of osteosarcoma by gene expression and cytogenetic analyses

The metastatic behavior of osteosarcoma by gene expression and cytogenetic analyses

Author Salinas-Souza, Carolina Autor UNIFESP Google Scholar
De Oliveira, Renato Autor UNIFESP Google Scholar
De Seixas Alves, Maria Teresa Autor UNIFESP Google Scholar
Garcia Filho, Reynaldo Jesus Autor UNIFESP Google Scholar
Petrilli, Antonio Sergio Autor UNIFESP Google Scholar
Toledo, Silvia Regina Caminada de Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract Osteosarcoma is a malignant bone tumor with high metastatic potential. Metastasis at diagnosis is the most significant prognostic factor in predicting the clinical outcome of osteosarcoma. We compared the gene expression of metastases that were present at the time of initial diagnosis to those developed later in the course of the disease. We used quantitative real-time polymerase chain reaction to evaluate the gene expression of MDM2, CXCR4, RANKL, RB1, and OSTERIX in 98 samples of osteosarcoma taken from 47 patients (74 metastases and 24 primary tumors) and 30 nonmalignant lung tissues surrounding osteosarcoma metastases. in addition, we investigated the copy number changes of RB1 and MDM2 genes in 12 primary cultures of pulmonary metastases of osteosarcoma, using interphase fluorescence in situ hybridization. Metastases from metastatic patients at diagnosis were characterized by low expression of RB1 and RANKL (P = .0009 and P = .0109, respectively) and overexpression of CXCR4 and MDM2 (P = .0389 and P = .0325, respectively). the loss of RANKL and gain of CXCR4 could also be detected in the primary tumors of metastatic patients at diagnosis (P = .0121 and P = .0264, respectively). Thus, some early genetic events such as the loss of RANKL and the gain of CXCR4 expressions probably facilitate the metastatic progression concomitant with the primary tumor establishment, supporting the role of the CXCR4 receptor in directing osteosarcoma metastases to the lung. On the other hand, late events such as the loss of RB1 and gain of MDM2, crucial regulators of cell cycle, appear to be related to the final mechanisms contributing to the metastatic establishment of osteosarcoma. (c) 2013 Elsevier Inc. All rights reserved.
Keywords Osteosarcoma
Gene expression
Lung metastasis
Cell culture
Fluorescence in situ hybridization
MDM2
CXCR4
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grupo de Apoio ao Adolescente e a Crianca com Cancer (GRAACC/UNIFESP; São Paulo, Brazil)
Date 2013-10-01
Published in Human Pathology. Philadelphia: W B Saunders Co-Elsevier Inc, v. 44, n. 10, p. 2188-2198, 2013.
ISSN 0046-8177 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 2188-2198
Origin http://dx.doi.org/10.1016/j.humpath.2013.04.013
Access rights Closed access
Type Article
Web of Science ID WOS:000325037000028
URI http://repositorio.unifesp.br/handle/11600/36816

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