Ultraviolet-radiation-induced inflammation promotes angiotropism and metastasis in melanoma (Nature, 2014, 507(7490):109-113)

Topic: Ultraviolet-radiation-induced inflammation promotes angiotropism and      

      metastasis in melanoma

Date: 2014/ 10/ 07

Reporter: Hsu Wen-Li

The source: Nature 507, 109–113, 2014

Advisor: Yan Shian-Jang

ABSTRACT

Intermittent intense ultraviolet (UV) is the major etiologic factor for developing malignant melanoma. UV radiation induces tumour-initiating DNA mutations in melanoma; however, so far how the microenvironmental effects of UV irradiation affects melanoma pathogenesis has all been independently established. To this end, a genetically engineered mouse model is performed to investigate the metastatic progression; the results point out repetitive UV exposure of primary cutaneous melanomas promotes metastasis facility but no difference in tumour initiating effects. UV irradiation increases the expansion of tumour cells along abluminal blood vessel surfaces and the number of lung metastase, which are due to UV-induced neutrophilic inflammatory response. The effect is relative tothe release of high mobility group box 1 (HMGB1) from Toll-like receptor (TLR) 4/MYD88 signaling which is driven by UV-damaged epidermal keratinocytes not TLR3/TRIF. Besides, UV promotes the migration facility of melanoma cells with the activated angiogenesis, towards endothelial cells utilizing selective motility to their surfaces. UV induced the innate immune system stimulates the interaction between melanoma and endothelial cell, contributes to angiotropism, which not only displays a potential mechanism of metastasis but also enhances the level of intravasation and haematogenous dissemination in human melanomas. Conclusively, our study indicates that UV damaged primary human melanomas frequently accompany with abundant neutrophils and reactive angiogenesis, displaying angiotropism and a high risk for metastases.

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