Trans‐homophilic interaction of CADM1 promotes organ infiltration of T‐cell lymphoma by adhesion to vascular endothelium

Abstract

The initial step of organ infiltration of malignant cells is the interaction with host vascular endothelial cells, which is often mediated by specific combinations of cell adhesion molecules. Cell adhesion molecule 1 (CADM1) is overexpressed in adult T‐cell leukemia/lymphoma (ATL) and provides a cell‐surface diagnostic marker. CADM1 promotes the adhesion of ATL cells to vascular endothelial cells and multiple organ infiltration in mice. However, its binding partner on host cells has not yet been identified. In this study, we show that CADM1 promotes transendothelial migration of ATL cells in addition to the adhesion to vascular endothelial cells. Moreover, CADM1 enhances liver infiltration of mouse T‐cell lymphoma cells, EL4, after tail vein injection, whereas a CADM1 mutant lacking adhesive activity did not. Among the known CADM1‐binding proteins expressed in primary endothelial cells, only CADM1 and CADM4 could induce morphological extension of ATL cells when plated onto glass coated with these proteins. Furthermore, CADM1‐mediated liver infiltration of EL4 cells was canceled in conventional and vascular endothelium‐specific Cadm1 knockout mice, whereas it was not canceled in Cadm4 knockout mice. These results suggest that CADM1 on host vascular endothelial cells is required for organ infiltration of ATL and other T‐cell lymphomas expressing CADM1.

IGSF3 is a homophilic cell adhesion molecule that drives lung metastasis of melanoma by promoting adhesion to vascular endothelium

“…26 Moreover, homophilic or heterophilic binding of PECAM1, JAM-C, MCAM, AMIGO2, and CADM1 enhances tumor-endothelium adhesion. 11,[27][28][29][30] Our study reveals IGSF3 as another example of such IgCAMs (Figure 5). Some of these IgCAMs are considered to regulate organotropism based on their organ-specific endothelial expression.…”

“…After 24 h, the extracted lungs were immunostained with anti‐CD31 Ab to visualize vascular endothelial cells as previously described. 11 The subcutaneous tumor formation assay was carried out by injecting a suspension of 5 × 10 5 cells in 200 μL PBS into both flanks of the mice. Tumor diameters were measured twice a week, and the tumor volume was calculated as 1/2 × length × width 2 .…”

“…After 24 h, the extracted lungs were immunostained with anti-CD31 Ab to visualize vascular endothelial cells as previously described. 11 The subcutaneous tumor formation assay was carried out by injecting a suspension of 5 × 10…”

IGSF3 is a homophilic cell adhesion molecule that drives lung metastasis of melanoma by promoting adhesion to vascular endothelium

“…For extravasation studies, mice were injected with 2 × 10 5 EGFP-expressing cells in 200 μL of PBS into the tail vein. After 24 h, the extracted lungs were immunostained with anti-CD31 antibody to visualize vascular endothelial cells as previously described 11 . The subcutaneous tumor formation assay was performed by injecting a suspension of 5 × 10 5 cells in 200 μL PBS into both flanks of the mice.…”

Secondary Budd–Chiari syndrome caused by adult T‐cell leukemia/lymphoma

“…CADM1 is known to play a role in intercellular adhesion, and we hypothesize that CADM1 can promote the adhesion of ATL cells to endothelial cells of the liver, contributing to massive invasion into the hepatic veins. 4 Budd-Chiari syndrome and IVC syndrome can overlap. IVC syndrome is a set of signs and symptoms that signify obstruction or compression of the IVC, and the present case falls within the category of IVC syndrome.…”