Gene expression of neurochemical stress and protumor markers in osteosarcoma, adjacent tissue, and healthy bone




Cindy Bandala, Laboratorio de Neurociencia Traslacional Aplicada a Enfermedades Crónicas y Emergentes, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México, México
Adrián Sánchez-Rojas, Laboratorio de Neurociencia Traslacional Aplicada a Enfermedades Crónicas y Emergentes, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México, México
Jazmín Carro-Rodríguez, Laboratorio de Neurociencia Traslacional Aplicada a Enfermedades Crónicas y Emergentes, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México, México
Valentín Martínez-López, Unidad de Ingeniería de Tejidos, Terapia Celular y Medicina Regenerativa, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Ciudad de México, México
Eréndira Estrada-Villaseñor, Servicio de Patología, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Ciudad de México, México
Modesto Gómez-López, Laboratorio de Biología Molecular del Proceso Inflamatorio, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México, México


Background: Osteosarcoma (OS) is a malignant bone neoplasm with a high recurrence rate. Currently, tumor-free margins are determined through histopathological analysis. The expression of genes related to proliferation, angiogenesis, metastasis, and neurochemical stress may represent early markers of transformation in tissue considered “tumor-free”. Objective: To compare the gene expression of β-adrenergic receptors 1 and 2 (ADRB1 and ADRB2), dopamine receptor D2 (DR2), vascular endothelial growth factor receptor 2 (VEGFR2), Ki-67, fibronectin (Fn), and matrix metalloproteinases 2, 9, and 14 (MMP-2, MMP-9 and MMP-14) in OS tissue, adjacent tissue, and non oncological bone (control). Materials and methods: Ten samples per group (OS, adjacent, and control) were obtained from patients treated at the Luis Guillermo Ibarra Ibarra National Institute of Rehabilitation. Each sample was processed for primary culture and gene expression analysis via polymerase chain reaction. Results: OS tissues and primary cultures presented lower expression of DR2 and higher expression of ADRB1, ADRB2, Ki-67, VEGFR2, MMP-2, MMP-9, and MMP-14 than adjacent and control tissues did (p < 0.05). Compared with control tissues, adjacent tissues presented greater expression of Ki-67 and lower expression of DR2 and Fn compared with control (p < 0.05). In primary cultures, MMP-9 and MMP-14 expression was greater in adjacent tissues than in control (p < 0.05). Conclusions: The gene expression of DR2, Fn, Ki-67, MMP-9, and MMP-14 may serve as early indicators of tumor transformation in tissues adjacent to OS, representing a complementary finding to histopathological evaluation for the accurate definition of tumor-free margins.



Keywords: Osteosarcoma. Gene expression. Beta-1 adrenergic receptor. Beta-2 adrenergic receptor. Dopamine D2 receptor. Protumoral markers. Tumor-free margins.




  •   Version en español

  •   Add to Mendeley