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

Abstract

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 Ca 2 þ /Mg 2 þ -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.

Tumor Suppressor in Lung Cancer-1 Is a Prognostic Predictor for the Recurrence and Progression of Non-Muscle-Invasive Bladder Cancer

“…As the positive control, we found that TSLC1 expression was high in normal bladder tissue and the expression was restricted to urothelial cells (fig. 1d), consistent with previous report [26]. …”

Aberrations of a cell adhesion molecule CADM4 in renal clear cell carcinoma

“…9,10 We have reported that CADM4 is expressed in the brain, lung, large and small intestines and urinary organs and that CADM4 could act as a tumor suppressor in prostate cancer. 11 We have also demonstrated that CADM1 associates with an actin-binding protein, 4.1B/DAL-1, through the FERM-binding motif in the cytoplasmic domain. 12 Frequent loss of 4.1B in lung adenocarcinoma, breast cancer and meningioma suggested that 4.1B could be a tumor suppressor.…”

“…11 The CADM1 antibodies used in this study were two rabbit polyclonal antibodies (pAbs) against the cytoplasmic domain, C-18, 22 and number 6 and a chicken monoclonal antibody (mAb) against the ectodomain, 3E1. 23 A rabbit pAb against 4.1B/DAL-1 was described previously.…”

“…We have previously reported that CADM4 could be a tumor suppressor candidate in prostate cancer on the basis of the frequent loss of CADM4 expression (6 of 9) in primary prostate cancer as well as the suppression of tumor-forming activity by CADM4 in a prostate cancer cell line, PPC-1. 11 As shown previously, CADM4 is expressed in a quite unique spectrum of tissues, such as the brain, lung, large and small intestines and urinary organs, including the kidney, ureter, bladder and prostate. The involvement of CADM4 in both RCCC and prostate cancer suggests that the malignant tumors of uroepithelial origin might have a common target cascade, at least in part, in their carcinogenic processes.…”

Epigenetic Silencing of a Proapoptotic Cell Adhesion Molecule, the Immunoglobulin Superfamily Member IGSF4, by Promoter CpG Methylation Protects Hodgkin Lymphoma Cells from Apoptosis

“…IGSF4 encodes a transmembrane protein whose extracellular domain shows close homology to the immunoglobulin superfamily cell adhesion molecules (Ig-CAM), particularly with the neural cell adhesion molecules, N-CAM1 and N-CAM2, 10 and the prostate tumor-suppressor TSLL2/IGSF4C. 11 Silencing of IGSF4, 12 is frequently observed in solid tumors including lung, 13 prostate, 10 pancreatic, gastric, breast, nasopharyngeal, 14 and cervical cancers, 15,16 as well as nasal NK/T-cell lymphoma. 17 Restoration of IGSF4 expression decreases epithelial cell scattering and tubulogenesis and suppresses lung cancer metastasis in nude mice, 13,18 -20 IGSF4 also reduces the anchorage-independent growth and tumorigenicity of cervical cancer cells.…”