Oridonin inhibits migration, invasion, adhesion and TGF-β1-induced epithelial-mesenchymal transition of melanoma cells by inhibiting the activity of PI3K/Akt/GSK-3β signaling pathway.
We found that anti-LAP antibody, which targets the latency-associated peptide (LAP)/transforming growth factor-β (TGF-β) complex on T<sub>regs</sub> and other cells, enhances antitumor immune responses and reduces tumor growth in models of melanoma, colorectal carcinoma, and glioblastoma.
In summary, our results integrated TGF-β1 signals to SKP2 via Akt1 and c-Myc during EMT, and provided, to our knowledge, a previously unreported mechanistic molecular event for TGF-β1-induced metastasis in human melanoma.
The induction of transforming growth factor beta1, 2 and 3 as well as BMP4 and BMP7 expression in malignant melanoma has been reported before, whereas the expression of an important modulator of these molecules, connective tissue growth factor (CTGF), has not been investigated in melanomas until now.
It was found that TNFA -238 GA, TGFB1 -509 CT, -800 GG, IFNG +874 AT, IL6 -174 GG, IL10 -1082 GA genotypes were significantly decreased, while TNFA -238 AA, -857 CC, TGFB1 -509 TT, IFNG +874 AA, IL6 -174 CC, IL10 -1082 AA, -819 TT, -592 AA genotypes were significantly increased, in MM.
This TGF-beta1-induced IL-8 expression could be an amplification cascade responsible for overexpression of IL-8 in human melanoma and one of potential mechanisms by which TGF-beta1 promotes angiogenesis, growth, and metastasis of human melanoma.
The induction of transforming growth factor beta1 (TGF-beta1), TGF-beta2, and TGF-beta3 expression in malignant melanoma has been reported before, whereas the expression of related bone morphogenic protein (BMP) molecules has not been analyzed in melanomas until now.
These data suggest that remodeling of the neighboring stroma, which provides a supporting scaffolding and a positive feedback stimulation of tumor growth, is an important function of TGF-beta1 in melanoma.
Whereas two glioblastoma cell lines expressed both TGF-beta 1 and G-TsF/TGF-beta 2 mRNA, one melanoma and neuroblastoma cell lines showed only TGF-beta 1 mRNA which in the case of the neuroblastoma required cycloheximide treatment for its detection.