<i>In vivo</i> xenograft experiments also demonstrated that MSCs promoted differentiation into CAFs through CXCR4/TGF-β1 signaling in either primary tumor tissues or hepatic metastatic tissues of CRC.<b>Conclusion</b>: Our studies have revealed the essential role of CXCR4/TGF-β1 axis playing in the transformation of tumor microenvironment by mediating MSCs differentiation into CAFs, promoting CRCs growth and metastasis.
Transforming growth factor-beta1 (TGF-beta1) is overexpressed in a variety of malignant epithelial tumors and was suggested to be a marker of colorectal cancer.
As this is the first study about the influence of the polymorphisms in the TGFB1 pathway on CRC progression, further studies in large independent cohorts are warranted.
For VEGFR1, PDGFRA and TGFB1 we didn't find significantly differential expression between any of the studied groups, even if increased levels were observed in both CRC and AP vs CTR.
Frequent somatic mutations in a polyadenine (poly(A)) tract and two GT repeats within the coding region of the transforming growth factor beta (TGFbeta) receptor II (RII) gene were reported in colorectal cancers with MSI.
Ginsenoside Rb2 could inhibit EMT of colorectal cancer cells through the TGF-β1/Smad signaling, and might be a potential candidate for the treatment of colorectal cancer.
However, C allele of TGF-β1 -509 C > T and A allele of -800 G > A were associated with increased risk of colorectal cancer (CRC), and OR (95%CI) was 1.23 (0.99-1.52) for CC vs. TT for -509 C > T and 6.64 (3.46-12.72) for A carriers vs. GG.
However, only limited information is available on genetic variation in the TGFB1 gene and its relationship to circulating levels and risk of colorectal cancer.
Human CRC cell lines HT-29 and SW480 were treated by TPL for 24 h in the presence or absence of epithelial-to-mesenchymal transition (EMT) inducer TGF-β1.
In a mouse hepatic metastasis model, treated with AMD3100 or Cy blocked the metastatic potential of HCT116 cells and the hepatic CAFs differentiation.<b>Conclusions</b>: These results indicated that CXCR4/TGF-β1 axis plays an important role in CRC liver metastasis through mediating HSCs differentiation into CAFs, providing preclinical evidences that blockade of the axis might be beneficial for anti-metastasis therapy in CRC.