Assessing the Role of the VCAM1-VLA4 Interaction in Macrophage Polarization in Pulmonary Metastatic Osteosarcoma

Abstract Macrophages are key members of the innate immune system involved in phagocytosis, antigen presentation and other immunological functions. also important players response to tumor. Their polarization states determine role that they play tumor microenvironment (TME) generally regarded as M1-like M2-like associated macrophages (TAMs). Subsequently, TME influences how function environment. Osteosarcoma is an aggressive solid about 20% patients present with lung metastasis at time diagnosis. Pulmonary metastatic osteosarcoma has a low 5-year survival rate less than 20%. The ability for metastasize lungs due, part, by expression Vascular Cell Adhesion Molecule 1 (VCAM1) on its surface. However, it not well-known this protein contributes metastasis. We speculate binding interaction between VCAM1 integrin α4β1 (VLA4) some process. Recently, our lab obtained preliminary data suggesting one methods osteosarcomas use shape into pro-tumor (M2-like) phenotype through surface VLA4 macrophages. Our shows upregulates enzyme Arginase 1, (Arg1) well-accepted marker M2-polarized phenomenon may be, regulated protein, suppressor cytokine signaling (SOCS1), inhibits phosphorylation transcription factor, signal transducer activator (STAT1); thus, allowing STAT3 phosphorylate upregulate M2-associated genes such Arg1. St Baldricks Foundation, Keira Kilbane Steven G. AYA Cancer Research Fund, Theresa & Stuart F. Kline Family Foundation