Primary tumorectomy promotes angiogenesis and pulmonary metastasis in osteosarcoma-bearing nude mice

Abstract

PURPOSE:To investigate the effect of primary tumorectomy on angiogenesis and pulmonary metastasis in osteosarcoma-bearing nude mice. METHODS:Osteosarcoma was introduced to nude mice via subcutaneous injection of MG-63 cells. One hundred and eighty osteosarcoma-bearing mice were used equally in 3 parallel experiments. The effect of tumorectomy (TR) on the expression of vascular endothelial growth factor (VEGF) and endostatin was investigated by ELISA. Meanwhile, the effect on angiogenesis was evaluated by Matrigel plug assay, and pulmonary metastasis assessed by calculating the metastatic foci. Sham-operation (SO) and untreated (UT) groups served as controls. RESULTS:The VEGF (TR: 79.55 ± 7.82 pg/mL vs. SO: 110.01 ± 5.69 pg/mL, UT: 123.50 ± 10.41 pg/mL; p < 0.01) and endostatin (TR: 47.09 ± 6.22 ng/mL vs. SO: 117.64 ± 7.39 ng/mL, UT: 126.73 ± 6.55 ng/mL; p<0.01) were down-regulated significantly after tumorectomy, and angiogenesis was significantly promoted simultaneously. The incidence of pulmonary metastatic foci was 80.0% in the TR group, 40.0% in the SO group and 35.0% in the UT group. CONCLUSION:Primary tumorectomy can down-regulate the expression of VEGF and endostatin and promote angiogenesis which leads to the acceleration of pulmonary metastasis. These findings imply that anti-angiogenic treatment can be considered after primary tumorectomy.Key words: Osteosarcoma. Neplasm Metastasis. Vascular Endothelial Growth Factor A. Endostatins. Tumor Resistance. Mice. Primary tumorectomy promotes angiogenesis and pulmonary metastasis in osteosarcoma-bearing nude mice

Matrigel: From discovery and ECM mimicry to assays and models for cancer research

“…It was found that nude mice after primary tumorectomy had decreased VEGF and endostatin levels, increased angiogenesis in the BME/Matrigel plug assay, and an increase in the incidence of pulmonary metastatic lesions. These findings suggest that antiangiogenesis therapy might be more effective after primary tumorectomy [146]. An additional use of the plug is as a vascularized organoid to study tumor extravasation.…”

Effect of concurrent metastatic disease on survival in children and adolescents undergoing lung resection for metastatic osteosarcoma

“…Overall survival and event-free survival from completion of first thoracotomy for Group B patients stratified by the presence or absence of extrapulmonary metastases at diagnosis tumor [22,23]. These findings suggest that primary osteosarcoma tumors prevent metastatic growth via angiogenesis inhibition.…”

Expression and Clinical Significance of ACTA2 in Osteosarcoma Tissue

“…With 80%-90% of patients with osteosarcoma clinically considered to have micro-metastases and with only 15%-20% of patients found to have metastatic lesions at clinically detectable diagnosis, which occur predominantly in the lungs (85%-90%) but sometimes in the bones or lymph nodes [1,2], pulmonary metastases remain the most important cause of treatment failure in osteosarcoma. It has been noted that the significant results of Gene Ontology (GO) enrichment analysis of differentially expressed genes (DEGs) showed that the DEGs were mainly enriched in the positive regulation of the RNA polymerase II promoter in transcription, angiogenesis, and inflammatory response in the bioprocessome, yielding results closely related to the currently reported angiogenesis in osteosarcoma metastasis [10,11].…”