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However, the mechanisms that produce metastatic stem cells in preneoplastic liver tissue are not well understood. Chronic inflammation, according to We hypothesized, is a key contributor of the transformation of genetically defective liver stem cells into highly metastatic liver cancer cells in premalignant liver tissue. LSCs derived from preneoplastic livers of 2SP+/- mice treated with interleukin-6 were highly tumorigenic and metastatic, whereas those derived from WT mice treated with pIL6 had significantly less proliferation and no tumorigenic characteristics, whereas those derived from pIL6 mice treated with pIL6 were highly tumorigenic and metastatic. LSCs not only demonstrated nuclear localization of Twist and Slug as signs of epithelial-mesenchymal transition, but also constitutive activation of nuclear factor kappa B. NFB in IL6:2SP+/- LSCs was inactivated by transforming growth factor - activated kinase 1, which is linked to poor HCC and interleukin-6 expression and poor growth. From normal to cirrhotic to HCC tissues from human patients, the number of constitutively activated NFB has increased dramatically.
Source link: https://doi.org/10.1002/hep.28951
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