Involvement of chemokine receptor 4/stromal cell-derived factor 1 system during osteosarcoma tumor progression

Eliana Perissinotto, Giuliana Cavalloni, Francesco Leone, Valentina Fonsato, Stefania Mitola, Giovanni Grignani, Nadia Surrenti, Dario Sangiolo, Federico Bussolino, Wanda Piacibello, Massimo Aglietta

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)490-497
Number of pages8
JournalClinical Cancer Research
Volume11
Issue number2 I
Publication statusPublished - Jan 15 2005

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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