骨肉瘤
间质细胞
癌症研究
转移
基质细胞衍生因子1
CXCR4型
趋化因子受体
归巢(生物学)
医学
骨髓
生物
免疫学
趋化因子
病理
受体
癌症
内科学
生态学
作者
Eliana Perissinotto,Giuliana Cavalloni,Francesco Leone,Valentina Fonsato,Stefania Mitola,Giovanni Grignani,Nadia Surrenti,Dario Sangiolo,Federico Bussolino,Wanda Piacibello,Massimo Aglietta
标识
DOI:10.1158/1078-0432.490.11.2
摘要
Abstract Despite intensive chemotherapy and surgery treatment, lung and bone metastasis develop in about 30% of patients with osteosarcoma. Mechanisms for this preferential metastatic behavior are largely unknown. We investigated the role of the chemokine receptor 4 (CXCR4)/stromal cell–derived factor 1 (SDF-1) system to drive the homing of osteosarcoma cells. We analyzed the expression of the CXCR4 and SDF-1 proteins on several osteosarcoma cell lines and the effects of SDF-1 on migration, adhesion, and proliferation of these cancer cells. In vitro assays showed that the migration of osteosarcoma cells expressing CXCR4 receptor follows an SDF-1 gradient and that their adhesion to endothelial and bone marrow stromal cells is promoted by SDF-1 treatment. Moreover, the production of matrix metalloproteinase-9 is increased after SDF-1 exposure. We finally proved in a mouse model our hypothesis of the CXCR4/SDF-1 axis involvement in the metastatic process of osteosarcoma cells. Development of lung metastasis after injection of osteosarcoma cells was prevented by the administration of a CXCR4 inhibitor, the T134 peptide. These data show a possible explanation for the preferential osteosarcoma metastatic development into the lung, where SDF-1 concentration is high, and suggest that molecular strategies aimed at inhibiting the CXCR4/SDF-1 pathway, such as small-molecule inhibitors or anti-CXCR4 antibodies, might prevent the dissemination of osteosarcoma cells.
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