Journal
CELLS
Volume 11, Issue 23, Pages -Publisher
MDPI
DOI: 10.3390/cells11233922
Keywords
vascular cell adhesion molecule-1; VLA4; immunotherapy; pediatric cancer; anti-integrin therapy; osteosarcoma
Categories
Funding
- St. Baldrick's Foundation-Osteosarcoma Collaborative Impact Award
- Pediatric Cancer Research Foundation
- Tim & Sandy Wulliger Family Fund
- Wulliger Foundation
- Karen & Alan Krause Pediatric Immunotherapy Innovation and Education Fund
- Keira Kilbane Foundation Cancer Discovery Fund
- Steven G. AYA Cancer Research Fund
- MIB Agents
- I'm Not Done Yet Foundation
- NCI/NIH R21 Award [R21CA218790]
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Vascular Cell Adhesion Molecule-1 (VCAM-1) is a membrane protein with critical physiological functions in cellular immune response. It can be cleaved into a soluble form (sVCAM-1) and elevated concentrations of sVCAM-1 have been found in the peripheral blood of cancer patients. The VCAM-1/VLA-4 signaling plays a vital role in tumor metastasis and therapy resistance.
Vascular Cell Adhesion Molecule-1 (VCAM-1; CD106) is a membrane protein that contributes critical physiologic functional roles in cellular immune response, including leukocyte extravasation in inflamed and infected tissues. Expressed as a cell membrane protein, VCAM-1 can also be cleaved from the cell surface into a soluble form (sVCAM-1). The integrin alpha 4 beta 1 (VLA-4) was identified as the first major ligand for VCAM-1. Ongoing studies suggest that, in addition to mediating physiologic immune functions, VCAM-1/VLA-4 signaling plays an increasingly vital role in the metastatic progression of various tumors. Additionally, elevated concentrations of sVCAM-1 have been found in the peripheral blood of patients with cancer, suggesting the tumor microenvironment (TME) as the source of sVCAM-1. Furthermore, over-expression of VLA-4 was linked to tumor progression in various malignancies when VCAM-1 was also up-regulated. This review explores the functional role of VCAM-1 expression in cancer metastasis and therapy resistance, and the potential for the disruption of VCAM-1/VLA-4 signaling as a novel immunotherapeutic approach in cancer, including osteosarcoma, which disproportionately affects the pediatric, adolescent and young adult population, as an unmet medical need.
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