Malignant Transformation in Skin is Associated with the Loss of T-Cadherin Expression in Human Keratinocytes and Heterogeneity in T-Cadherin Expression in Tumor Vasculature

T-Cadherin Stimulates Melanoma Cell Proliferation and Mesenchymal Stromal Cell Recruitment, but Inhibits Angiogenesis in a Mouse Melanoma Model

“…Expression of T-cadherin was reduced in psoriatic samples (Zhou et al, 2003) and was down-regulated or completely absent in invasive cutaneous squamous cell carcinoma (Takeuchi et al, 2002a) and in basal cell carcinoma of the skin (Takeuchi et al, 2002b). Data obtained in our lab supported these findings and confirmed that T-cadherin expression was not changed if cells maintained the attachment to the basal membrane in the lesions characterized by slow or controlled keratinocytes growth (keratoacanthoma, psoriasis, actinic keratosis and superficial basalioma) (Rubina et al, 2012). However, T-cadherin expression in keratinocytes was downregulated upon tumor progression in basosquamous cell carcinoma, squamous cell carcinoma and in some cases of basal cell carcinoma, i.e.…”

“…In human hepatocellular carcinoma (НСС) T-cadherin was also upregulated in intratumoral capillary endothelial cells and this increase соrrеlаtеd with tumor growth and metastasis (Adachi et al, 2006). Data obtained in our lab indicated that in pre-malignant skin lesions all blood vessels uniformly expressed T-cadherin (Rubina et al, 2012). The aberrant expression of T-cadherin and vascular markers was detected in aggressively developing skin tumors such as basosquamous cell carcinoma, squamous cell carcinoma and in some cases of basal cell carcinoma.…”

“…However, T-cadherin expression in keratinocytes was downregulated upon tumor progression in basosquamous cell carcinoma, squamous cell carcinoma and in some cases of basal cell carcinoma, i.e. tumors with high proliferative, invasive, and metastatic potential (Rubina et al, 2012).…”

“…In some reports, T-cadherin was regarded as a tumor suppressor and its downregulation was associated with tumor progression. Downregulation of T-cadherin was shown to be associated also with tumorogenicity in breast (Riener et al, 2008), lung (Sato et al, 1998) T-cadherin is expressed in the basal layer of keratinocytes, in melanocytes and in vascular cells of the dermal blood vessels in the normal skin (Zhou et al, 2002;Kuphal et al, 2009;Rubina et al, 2012). However, its expression was consequently lost upon cell transformation and tumor progression in pre-malignant skin lesions and in non-melanoma skin cancer.…”

Effects of T-cadherin expression on B16F10 melanoma cells

“…T-cadherin has been shown to have diverse roles in physiology and pathophysiology, including as a negative guidance cue for motor axon projections, tumor suppressor factor in various types of cancer, atypical lipoprotein-binding protein and stimulator of angiogenesis (44–46). Hence, in various studies T-cadherin has been shown to be involved in the regulation of proliferation, apoptosis and angiogenesis in normal tissues, as well as tumor growth (47). …”