Bone deposition, bone resorption, and osteosarcoma.
Bone deposition and bone resorption are ongoing dynamic processes, constituting bone remodeling. Some bone tumors, such as osteosarcoma (OS), stimulate focal bone deposition. OS is the most common primary bone tumor in children and young adults. A complex network of genes regulates bone remodeling and alterations in its expression levels can influence the genesis and progression of bone diseases, including OS. We hypothesized that the expression profiles of bone remodeling regulator genes would be correlated with OS biology and clinical features. We used real-time PCR to evaluate the mRNA levels of the tartrate-resistant acid phosphatase (ACP5), colony stimulating factor-1 (CSF1R), bone morphogenetic protein 7 (BMP7), collagen, type XI, alpha 2 (COL11A2), and protein tyrosine phosphatases zeta 1 (PTPRZ1) genes, in 30 OS tumor samples and correlated with clinical and histological data. All genes analyzed, except CSF1R, were differentially expressed when compared with normal bone expression profiles. In our results, OS patients with high levels of COL11A2 mRNA showed worse overall (p = 0.041) and event free survival (p = 0.037). Also, a trend for better overall survival was observed in patients with samples showing higher expression of BMP7 (p = 0.067). COL11A2 overexpression and BMP7 underexpression could collaborate to OS tumor growth, through its central role in bone remodeling process.
Pediatrics Department, Pediatric Oncology Institute Grupo de Apoio ao Adolescente e à Criança com Câncer (GRAACC), Federal University of São Paulo, Rua Botucatu, 743, Floor 8 - Genetics Laboratory, Vila Clementino, São Paulo, SP 04023-062, Brazil. silviatoledo@graacc.org.br
Sílvia Regina Caminada
SR
Toledo
Indhira Dias
ID
Oliveira
Oswaldo Keith
OK
Okamoto
Marco Antonio
MA
Zago
Maria Teresa
MT
de Seixas Alves
Reynaldo Jesus Garcia
RJ
Filho
Carla Renata Pacheco Donado
CR
Macedo
Antonio Sergio
AS
Petrilli
D000135:Acid Phosphatase / Q000235:genetics; D000293:Adolescent; D001706:Biopsy; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics; D001859:Bone Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology; D001862:Bone Resorption / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002113:Calcification, Physiologic / Q000235:genetics*; D002648:Child; D024161:Collagen Type XI / Q000235:genetics; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D012516:Osteosarcoma / Q000235:genetics / Q000401:mortality / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000235:genetics; D016019:Survival Analysis; D000071681:Tartrate-Resistant Acid Phosphatase; D055815:Young Adult
D055419:Bone Morphogenetic Protein 7; C499319:COL11A2 protein, human; D024161:Collagen Type XI; D007527:Isoenzymes; D012333:RNA, Messenger; D016186:Receptor, Macrophage Colony-Stimulating Factor; C000605510:ACP5 protein, human; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; C516895:PTPRZ1 protein, human; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5