Abstract
Objective: A high prevalence of thyroid papillary cancer has been reported in Hepatitis C virus (HCV) positive patients. The aims of our study are to: 1) Investigate the mechanistic role of liver injury in thyroid malignancy progressions. 2) Study the immune-modulatory interactions between thyroid papillary carcinoma and hepatic-fibrosis.
Method: In vivo: Hepatic-fibrosis and thyroid carcinoma cell line were induced in nude mice. Fibrotic profile was estimated using RT-PCR and Western blots. Lymphocytes were stained for NK-activity. Liver injury, tumor mass, serum VEGF, estradiol, and T4 levels were assessed. Ex-vivo: Thyroid cell line was analyzed for proliferations by CFSE.
Results: Tumor groups excreted higher serum T4 levels. Hepatic-fibrosis increased tumor weight and size and serum T4 levels. In addition, animals with both tumor and hepatic-fibrosis had increased NK activity. Therefore, animals with tumors increased fibrosis in spite of increased NK activity; probably due to a direct effect through increased serum-free T4 excretions. Serum VEGF levels were significantly increased in the fibrotic groups. In vitro, lymphocytes harvested from fibrotic animals with thyroid tumors induction co-cultured with tumor cells led to a decrease in their proliferations as compared to tumor cells alone. This decrease could be attributed to the increase in NK activity.
Conclusion: Our results propose immune-modulatory interactions with hepatic fibrosis and T4 excreting thyroid tumor. Advanced fibrosis and tumor activity propagate each other in the presence of the anti- tumor and anti fibrotic effects of the increased NK activity. This interplay may explain increased risk of thyroid tumors in chronic HCV patients.
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