The Role of Integrins in Osteosarcoma

Abstract

Integrins are cell adhesion molecules that link the extracellular matrix to the cytoskeleton and play a critical role in diverse cellular processes including gene transcription, signal transduction, proliferation, differentiation, migration, and apoptosis. Integrinsare centralto cancer biology and have been implicated in the pathogenesis and metastasis of osteosarcoma (OS). Increased αvβ3 integrin expression is directly correlated to the metastatic potential of multiple human OS cell lines. Additionally, αvβ3 integrin interaction with FPRL-1 and TIMP-1 enhances both chemotactic and anti-apoptotic ability in OS cells. Likewise, β1 integrins enhance OS tumorinvasiveness and metastasis by mediating cellular migration in response to chemokine stimulation. In summary, integrins hold potential as novel therapeutic targets due to their critical role in regulating cellular adhesion to bone matrix and consequently OS pathogenesis. Although integrins have been thoroughly studied in pre-clinical settings, pharmacological inhibition of integrins has not been successfully translated to clinical practice and is still under evaluation to elucidate its safety and efficacy in human patients.