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Review
. 2022 Dec 4;11(23):3922.
doi: 10.3390/cells11233922.

Ectopic Tumor VCAM-1 Expression in Cancer Metastasis and Therapy Resistance

Kristen A VanHeyst  1   2   3 , Sung Hee Choi  2 , Daniel T Kingsley  4 , Alex Y Huang  1   2   3   4
Affiliations
Review

Ectopic Tumor VCAM-1 Expression in Cancer Metastasis and Therapy Resistance

Kristen A VanHeyst et al. Cells. .

Abstract

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 α4β1 (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.

Keywords: VLA4; anti-integrin therapy; immunotherapy; osteosarcoma; pediatric cancer; vascular cell adhesion molecule-1.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structures of human and mouse VCAM-1 isoforms. Red circles represent Ig-domains. Red arrows denote VLA4 (α4β1) binding sites on VCAM-1. Blue arrows denote α4β7 binding sites on VCAM-1.
Figure 2
Figure 2
Signaling crosstalk between isoforms of VCAM-1 on tumor surface and VLA4 on macrophages. VLA-4 is also expressed on certain tumors to facilitate metastasis and therapy resistance.
See this image and copyright information in PMC

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