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Osteosarcoma cells expressing VCAM-1 increase metastatic potential through VCAM-1-VLA-4 signaling axis on macrophages 3997

Year: 2025
Type: article
Abstract: Description Osteosarcoma (OS) is an aggressive bone cancer primarily found in children and young adults with a five-year survival rate that drops significantly in patients with metastatic disease. At diagnosis, around 20% of patients have lung metastases, reducing survival from 70% to 30%. We believe that an indicator of metastatic potential is the aberrant expression of Vascular Cell Adhesion Molecule 1 (VCAM-1) on the tumor surface as human OS tissues have been shown to overexpress this molecule; however, its precise role remains unclear. We hypothesize that the interaction between VCAM-1 on OS cells and its receptor, the α4β1 integrin (VLA-4) on macrophages, contributes to the ability of OS to metastasize. Our preliminary evidence suggests that tumorigenic effects of VCAM-1 are isoform dependent, and truncated VCAM-1 is critically important to metastasis. Our research model uses bone marrow-derived macrophages exposed to murine OS cell lines K7 and K7M2, the latter being highly metastatic. Early data show that VCAM-1-VLA-4 binding induces a pro-tumoral macrophage phenotype, upregulating Arginase 1, an M2 macrophage marker. Currently, we are investigating whether this effect is specifically driven by the truncated isoform and exploring the role it plays in the PI3K-AKT signaling pathway. By elucidating how VCAM-1-VLA-4 interactions drive macrophage polarization, we aim to identify novel therapeutic targets that could shift macrophage behavior and improve treatment outcomes in OS. Funding Sources T32 AI089474-11A Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)
DOI: 10.1093/jimmun/vkaf283.1733
Language: English
Subfield: Immunology
Open Access status: bronze
OpenAlex ID: W4416449486
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