Cell adhesion and prostate tumor-suppressor activity of TSLL2/IGSF4C, an immunoglobulin superfamily molecule homologous to TSLC1/IGSF4

The TSLL2/IGSF4C encodes an immunoglobulin (Ig) superfamily molecule showing significant homology with a lung tumor suppressor, TSLC1. The TSLL2 protein of 55 kDa is mainly expressed in the kidney, bladder, and prostate in addition to the brain. Here, we report the biological significance of TSLL2 in the urinary tissues. An immunohistochemical study reveals that TSLL2 is expressed at the cell-cell attachment sites in the renal tubules, the transitional epithelia of the bladder, and the glandular epithelia of the prostate. Confocal microscopy analysis demonstrates that TSLL2 is localized in the lateral membranes in polarized Mardin-Darby canine kidney (MDCK) cells. TSLL2 forms homo-dimers and its overexpression induces aggregation of suspended MDCK cells in a Ca²⁺/Mg²⁺-independent manner, suggesting that it is involved in cell adhesion through homophilic trans-interaction. The TSLL2 gene is mapped on the chromosomal region 19q13.2, whose loss of heterozygosity has been frequently reported in prostate cancer. TSLL2 protein is lost in nine of nine primary prostate cancers and in a prostate cancer cell, PPC-1. Introduction of TSLL2 into PPC-1 strongly suppresses subcutaneous tumor formation in nude mice. These results suggest that TSLL2 is a new member of the Ig superfamily cell adhesion molecules and is a tumor-suppressor candidate in prostate cancer.