Role of CD44 in early hepatic carcinogenesis in Mdr2 knock-out mice

Background and aims: The membrane protein CD44 is upregulated in subpopulations of cancer cells and has been linked to cell proliferation and migration. In liver cancer mouse models, such as in diethylnitrosamin (DEN)-induced hepatocellular carcinoma (HCC) and in Mdr2-/- mice, CD44 is overexpressed in liver tumors. Importantly, DEN-treated Cd44-/- mice showed a significantly reduced tumor burden in comparison to controls. To further determine the role of CD44 in hepatic carcinogenesis, we induced HCC by in chronic cholestatic inflammation-induced in Mdr2-/-;Cd44-/- mice.

Methods: Mdr2-/-;Cd44-/- and Mdr2-/- mice were aged for 15 months and livers were analyzed for tumor development by histomorphology and immunohistochemistry for proliferation markers.

Results: Both Mdr2-/-;Cd44-/- and Mdr2-/- mice show only low numbers of HCC and the difference between groups was not significant. However, the number of foci of cellular alteration (FCA) that are considered as tumor precursor lesions, was significantly lower per liver in Mdr2-/-;Cd44-/- mice in comparison to controls (25.44 vs. 48.88; p=0.0188). Additionally, the number of FCAs larger than 1mm (2.44 vs. 6.25; p=0.0191) was also lower in CD44-deficient livers.

Conclusion: In the Mdr2-/- model of hepatic carcinogenenis, CD44 seems to play an important role in development and growth of tumor precursor lesions, though no effect on HCC development in this model was observed – possibly due to the low numbers of tumors overalls. Our data show that CD44 could play a key role in early hepatic tumorigenesis and could be a possible target to prevent HCC development.

Publication History

Article published online:
20 January 2025