The Role Of Slit2on The Chemical-induced Skin Carcinogenesis

The morbidity of Skin carcinoma increased rapidly on globle and peoplebecome more and more care about it. It is a big challenge to solve the treatment ofskin carcinoma.So, it is meaningful to reaserch cuntanous carcinoma.Slit, a member of the neuronal guidance cue, binds to Roundabout (Robo)receptors to modulate neuronal, leukocytic and endothelial migration. Slit had beenreported to have an important effect on tumor growth and metastasis. In the study, weevaluated the role of Slit2in skin tumor growth and invasion in mice by using atwo-step chemical carcinogenesis protocol. We firstly found that Slit2expression wascorrelated with the loss of basement membrane in the samples of human skinsquamous cell carcinoma at varying stages of disease progression. Slit2-Tg micesignificantly developed more skin tumors than the wild-type mice. Furthermore,significantly greater sizes of skin tumors occurred in Slit2-Tg mice than in thewild-type mice from week10after DMBA initiation until the end of the experiment.We also found that pathological development of the wild-type mice was postponedcompared with that of Slit2-Tg mice. To further investigate the mechanism ofincreasing tumors in Slit2-Tg mice, we analyzed the expression of BrdU in mouseskin lesions, and found the amount of BrdU-positive cells in skin lesions wassignificantly higher in Slit2-Tg mice than in wild-type mice. Histologic staining ofPAS and type IV collagen and the co-localization of Slit2and type IV collagendemonstrated that there were various extents of loss of the basement membrane in theskin lesions from Slit2-Tg mice in the stage of carcinoma in situ, but the basement membrane was well-defined in the wild-type mice.We also proved that the MMP-2expression significantly increased on each pathological stages on Slit2-Tg mice. Toconfirm the effect of slit2on basement membrane, we inhibit slit2/Robo1pathway byR5inhibitor of A431cell to investigate the cell invasion ability.we proved that slit2promote the cell invasion ability of A431cells.Taken together, our findings revealthat Slit2promotes DMBA/TPA-induced skin tumorigenesis by promote basementmembrane broken.