High expression of CD34 and α6-integrin contributes to the cancer-initiating cell behaviour in ultraviolet-induced mouse skin squamous cell carcinoma.

Squamous cell carcinoma caused by ultraviolet light exposure represents over 40% of all malignant diseases. It is one of the most commonly found human tumours. Tumour mass within squamous cell carcinoma consists of various cell types, including cancer-initiating cells that are responsible for tumour progression, metastasis and chemoresistance and implicated in clinical relapse. In the present study, we aimed to characterise whether the cell population with high CD34 and α6-integrin expression behave as cancer-initiating cells within ultraviolet-induced squamous cell carcinoma in mouse skin. CD34highα6-integrinhigh compared to CD34lowα6-integrinhigh cells isolated from ultraviolet-induced squamous cell carcinoma could propagate effectively by displaying greater tumour initiating and self-renewal abilities. Our study suggests that CD34highα6-integrinhigh cells act as initiators upon ultraviolet-induced skin squamous cell carcinoma.

Decreased expression of nemo-like kinase in melanoma is correlated with increased vascularity and metastasis.

Melanoma is a highly metastatic cancer, and its incidence has increased over the past several decades. Angiogenesis is associated with melanoma metastasis and a poor prognosis. Many genetic and epigenetic factors affecting tumour vascularization and metastasis have been investigated, despite the heterogeneity of cancer cells and the complicated mechanisms involved in melanoma. Nemo-like kinase (NLK) is a serine/threonine kinase regulating the transcription factor by negatively regulating Wnt and downstream vascular endothelial growth factor receptor 2 (VEGFR2) signalling. This study aimed to investigate whether NLK expression in melanoma correlates with VEGFR2-related angiogenesis and melanoma metastasis. Immunohistochemistry analysis using 175 biopsied tissues of melanoma patients showed that NLK is expressed in 73.7% of melanoma tissues, whereas 26.3% of the samples showed absent expression of NLK. In metastatic melanoma, the expression of NLK was significantly lower than that in primary melanoma (P = 0.002). Furthermore, tissues with a lower expression of NLK showed a higher microvessel density as detected by VEGFR2 expression compared with tissues showing higher NLK expression. These data suggest that reduced expression of NLK in melanoma correlates with VEGFR2-related microvessel formation and melanoma metastasis. This study showed that NLK may serve as a novel prognosis marker and revealed new mechanisms in melanoma metastasis.