Cross-talk of Ito(stellate) cell and preneoplastic and cancer cells of hepatocarcinogenesis

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Our finding during investigation terms are as follows ;(1) Choline deficient L-amino acid (CDAA) defined diet induced hepatocyte cell death and regeneration resulting in stellate cell activation leading to preneoplastic lesions surrounded with fibrosis. Treatment with anti-fibrotic agent e.g. prolyl 4-hydrohylase inhibitor lead to the inhibition of stellate cell activation resulting in the prevention of preneoplastic lesions with reduced fibrosis without the protection of cell death.(2) Treatment rats with Choline deficient L-amino acid (CDAA) defined diet induced the cell death and regeneration causing the activation of Kupffer and stellate cells which will produce TGF-beta 1 resulting in the perpetuation of fibrosis.(3) Addition of the supernatant of cultured hepatic cancer cells on stellate cells induced activation of MAP kinase pathway but addition of the supernatant of stellate cells on cancer cells did not change the cell cycle of cancer cell. Co-culture of stellate cells and cancer cells indicated that the movement of stellate cells to cancer cells. This result may suggest the prevention of cancer cell invasion by stellate cells. However further studies are necessary.(4) The activation of MAP kinase pathway by using adenovirus system revealed that the expression of MMP-9 is regulated mainly by ERK pathway and MMP-13 is regulated by P38 pathway independently.These results will give the new insight for the therapy of liver fibrosis as well as the mechanism of cancer metastasis.