Conclusively, it is the first study ever reporting that a pre-treatment of cells with TGF-β1 for experimental lung cancer metastasis mouse model may portray a more precise approach for the development of potential therapeutic treatments.
Inhibition of transforming growth factor-β1 (TGF-β1) using LY364947 and LY2109761 has been demonstrated to radiosensitize cancer cells such as breast cancer, glioblastoma, and lung cancer.
In conclusion, this study suggests that heavy smokers in this Korean population who have specific polymorphic variants, which have been associated with increased transcriptional activity of TGFB1, might be more vulnerable to lung cancer.
In cervical, gastric, colorectal, breast, and lung cancer, the cause of this failure is the inadequate expression of inducible nitric oxide synthase (iNOS), resulting from the inhibition of iNOS expression by TGF-beta1 at the mRNA level.
To test this hypothesis, we investigated the association of the TGF-beta1 -509C > T and 869T > C (L10P) polymorphisms and their haplotypes with the risk of lung cancer in a Korean population.
Here, we show that treatment with TGF-β1 (5 ng/mL) induced downregulation of cyclooxygenase-2 (COX-2), leading to reduced synthesis of prostaglandin E2 (PGE2), in human lung cancer A549 cells.
These results suggest that IL-10, TNF-alpha and TGF-beta1 gene polymorphisms may affect host susceptibility to lung cancer and the outcome of the patients.
Here, we report that neuropilin (NRP)-2, the high-affinity receptor for SEMA3F and a coreceptor for certain growth factors, is upregulated during TGF-β1-driven EMT in lung cancer cells.
Treatment with TGF-β1 facilitated migration of human lung cancer A549 cells, which was blocked by pretreatment with ecto-nucleotidase and P2 receptor antagonists.
Overall, no significant association was found between the TGFβ1T+869C polymorphism and lung cancer susceptibility under any genetic models in the total population (p > 0.05).
Finally, exposing A549 cells stably expressing ACE2 to DX600, an inhibitor of ACE2, recovered the sensitivity of lung cancer cells to TGF-β1-mediated induction of EMT.
We identified trihydroxyphenolic compounds as potent blockers of TGF-β1 responses (IC50 ~50 nM), Snail1 expression, and collagen deposition in vivo in models of pulmonary fibrosis and collagen-dependent lung cancer metastasis.
In conclusion, these results suggested that AA may inhibit TGF-β1-induced EMT in lung cancer through increased expression of E-cadherin, and inhibition of Snail, N-cadherin and vimentin expression.
While the addition of TGF-beta1 or retinoic acid to monkey normal lung bronchial 12MBr6 cells and human lung cancer NCI-H727 cells increased DENTT protein production, TGF-beta1 together with retinoic acid resulted in a more sustained increase in DENTT production than with TGF-beta1 or retinoic acid alone.
We also observed long-term TGFβ1 exposure leads to an enrichment of a sub-population of CD44<sup>+</sup> CD90<sup>+</sup> cells which represent CSCs in lung cancer cells.