Mechanism of Integrin-Mediated M2 Polarization of Tumor-Associated Macrophages by Metastatic Osteosarcoma
Mentor: Alex Huang
Our laboratory has identified VCAM-1 expression on pulmonary metastatic osteosarcoma as being a critical mediator between its interaction with its ligand, VLA4 (alpha4-beta1 integrin) on tumor-associated macrophages to functionally polarize the macrophages toward an M2 phenotype. This observation has led to a pending clinical trial (NCT03811886) using anti-alpha4 antibody, Natalizumab, for the treatment of unresectable pulmonary osteosarcoma. The POST award recipient will further investigate the molecular mechanisms linking integrin signaling to functional M2 polarization in tumor-associated macrophages. Working closely with a seasoned research scientist and an MD/PhD graduate student, the fellow will learn to cultivate primary macrophages and macrophage cell lines from mice and perform molecular signaling experiments downstream of VLA-4 ligation using Western blotting, RNAseq, fluorescent microscopy, flow cytometry and other related techniques.
