Expression of T-cadherin (CDH13, H-cadherin) in human brain and its characteristics as a negative growth regulator of epidermal growth factor in neuroblastoma cells

In the present study, we first examined the expression of T-cadherin in hum an CNS by northern blot analysis, immunohistochemical staining, and in situ hybridization. Northern blot analysis demonstrated expression of T-cadheri n in human adult cerebral cortex, medulla, thalamus, and midbrain. Immunohi stochemical staining with a newly generated monoclonal antibody, designated MA-511, revealed strong expression of T-cadherin in neural cell surface me mbrane and neurites in adult cerebral cortex, medulla oblongata, and nucleu s olivaris. Little or no expression of T-cadherin was found in spinal cord. We further examined T-cadherin expression in various developing nervous sy stems, and found that T-cadherin expression was lower in developing brain t han in adult brain. In situ hybridization revealed that neural cells in med ulla oblongata and nucleus olivaris, but not in spinal cord, possessed T-ca dherin molecules. We transfected T-cadherin-negative TGW and NH-12 neurobla stoma cells with a T-cadherin cDNA-containing expression vector. T-cadherin -expressing neuroblastoma cells lost mitogenic proliferative response to ep idermal growth factor. Epidermal growth factor is known to be required for proliferation of neural stem cells. This finding, together with those of th e present study, suggests that T-cadherin functions as a negative regulator of neural cell growth.