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. 2022 Jun 29;44(7):2879-2886.
doi: 10.3390/cimb44070198.

Correlation between Cancer Stem Cells, Inflammation and Malignant Transformation in a DEN-Induced Model of Hepatic Carcinogenesis

Chun-Chieh Wu  1   2 , Chien-Ju Lin  3 , Kong-Kai Kuo  4 , Wan-Tzu Chen  2 , Chen-Guo Ker  5 , Chee-Yin Chai  1   2 , Hung-Pei Tsai  6 , Sheau-Fang Yang  1   2
Affiliations

Correlation between Cancer Stem Cells, Inflammation and Malignant Transformation in a DEN-Induced Model of Hepatic Carcinogenesis

Chun-Chieh Wu et al. Curr Issues Mol Biol. .

Abstract

Chronic inflammation and cancer stem cells are known risk factors for tumorigenesis. The aetiology of hepatocellular carcinoma (HCC) involves a multistep pathological process that is characterised by chronic inflammation and hepatocyte damage, but the correlation between HCC, inflammation and cancer stem cells remains unclear. In this study, we examined the role of hepatic progenitor cells in a mouse model of chemical-induced hepatocarcinogenesis to elucidate the relationship between inflammation, malignant transformation and cancer stem cells. We used diethylnitrosamine (DEN) to induce liver tumour and scored for H&E and reticulin staining. We also scored for immunohistochemistry staining for OV-6 expression and analysed the statistical correlation between them. DEN progressively induced inflammation at week 7 (40%, 2/5); week 27 (75%, 6/8); week 33 (62.5%, 5/8); and week 50 (100%, 12/12). DEN progressively induced malignant transformation at week 7 (0%, 0/5); week 27 (87.5%, 7/8); week 33 (100%, 8/8); and week 50 (100%, 12/12). The obtained data showed that DEN progressively induced high-levels of OV-6 expression at week 7 (20%, 1/5); week 27 (37.5%, 3/8); week 33 (50%, 4/8); and week 50 (100%, 12/12). DEN-induced inflammation, malignant transformation and high-level OV-6 expression in hamster liver, as shown above, as well as applying Spearman’s correlation to the data showed that the expression of OV-6 was significantly correlated to inflammation (p = 0.001) and malignant transformation (p < 0.001). There was a significant correlation between the number of cancer stem cells, inflammation and malignant transformation in a DEN-induced model of hepatic carcinogenesis in the hamster.

Keywords: diethylnitrosamine; hepatocellular carcinoma; inflammation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
H&E staining of hamster liver: Portal inflammation was scored from 0 to 3 in week 7 (n = 5), 27 (n = 8), 33 (n = 8), 50 (n = 12) where a score of 0 indicated no portal inflammation (A); a score of 1 indicated ≤2 portal inflammation (B); a score of 2 indicated >2 portal inflammation (C); and a score of 3 indicated portal inflammation with interstitial sinusoidal inflammation (D).
Figure 2
Figure 2
The reticulin staining in hamster liver: we applied a score ranging from 0 to 2 in week 7 (n = 5), 27 (n = 8), 33 (n = 8), 50 (n = 12) where a score of 0 indicated no regenerated/malignant cell (A); a score of 1 indicated the presence of liver regenerated nodules (B); and a score of 2 denoted definitive liver malignancy (C).
Figure 3
Figure 3
The immunohistochemical staining of OV-6 in hamster liver in week 7 (n = 5), 27 (n = 8), 33 (n = 8), 50 (n = 12): a score of 0 indicated no positive cells (A); a score of 1 indicated ≤5 stem cells in one high power field (B); a score of 2 indicated ≥5 and <10 stems cells in one power field (C); a score of 3 indicated >10 stem cells in one power field (D). Scores 0 and 1 were considered low-level expression, whereas scores 3 and 4 were considered high-level expression.
Figure 4
Figure 4
Correlation between malignant transformation, cancer stem cells and inflammation. p value was calculated by Spearman’s correlation test.
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