CADM1/TSLC1 is a novel cell surface marker for adult T-cell leukemia/lymphoma.
CADM1/TSLC1 (Cell adhesion molecule 1/Tumor suppressor in lung cancer 1) is a cell adhesion molecule that was originally identified as a tumor suppressor in lung cancer. CADM1/TSLC1 expression is reduced in a variety of cancers via promoter methylation, and this reduction is associated with poor prognosis and enhanced metastatic potential. In contrast, we observed that CADM1/TSLC1 is highly and ectopically expressed in all primary adult T-cell leukemia/lymphoma (ATLL) cells and in most human T-cell leukemia virus type (HTLV)-1-infected T-cell and ATLL cell lines. No expression, however, was detected in CD4+T cells or in several other non-HTLV-1-infected leukemia cells. Moreover, we identified that high CADM1/TSLC1 expression plays an important role in enhanced cell-cell adhesion to the vascular endothelium, tumor growth and the ability of ATLL cells to infiltrate organs. We developed various antibodies as diagnostic tools to identify CADM1+ATLL cells. Using flow cytometry, we determined that CADM1/TSLC1 is present on the surface of ATLL cells. The percentage of CD4+CADM1+cells in the peripheral blood of HTLV-1 carriers and ATLL patients was highly correlated with the DNA copy number of HTLV-1 in lymphocytes. In particular, we identified the soluble form of CADM1/TSLC1 in the peripheral blood of HTLV-1 carriers and ATLL patients. Therefore, measurements of soluble CADM1/TSLC1 serum levels and the detection of CD4+CADM1+cells in the blood, when combined with standard diagnostic methods, would be useful for identifying and monitoring disease progression in HTLV-1 carriers. Such tests would provide increased accuracy and may aid in early diagnosis and in determining the effects of ATLL treatments.
Division of Tumor and Cellular Biochemistry, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, Japan.
Shingo
S
Nakahata
Kazuhiro
K
Morishita
D014408:Biomarkers, Tumor / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D002448:Cell Adhesion; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000097:blood*; D045744:Cell Line, Tumor; D015973:Gene Expression Regulation, Leukemic; D015368:Human T-lymphotropic virus 1; D006801:Humans; D007136:Immunoglobulins / Q000097:blood*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000097:blood* / Q000175:diagnosis / Q000628:therapy / Q000821:virology; D025521:Tumor Suppressor Proteins / Q000097:blood*
D014408:Biomarkers, Tumor; C403514:CADM1 protein, human; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D025521:Tumor Suppressor Proteins