Abstract 6141: Role of aldehyde dehydrogenase 1B1 in colon carcinogenesis in a newly developed mouse model

Abstract

Abstract Introduction: Aldehyde dehydrogenases (ALDH), particularly ALDH1B1 has been shown to have increased expression in both human and APCMin mice colorectal tumors. Studies have proposed the use of ALDH1B1 as a potential novel human colorectal tumor marker. Previous in vitro studies have shown that ALDH1B1 plays a critical role in colon carcinogenesis. The goal of this study is to understand the in vivo role of ALDH1B1 in colon carcinogenesis using a newly developed mouse model, APCMinAldh1b1−/− mice, through characterization of its phenotype in tumor growth and development, and elucidating the underlying potential molecular mechanisms. Methods: We generated APCMinAldh1b1−/-. At 12-14 weeks old, the experimental group APCMinAldh1b1−/- (n=6) and control group APCMinAldh1b1+/+ (n=7) were euthanized. Tumor counts, size and burden for each intestinal segments were recorded. H&E staining was performed and observed for tumor types and counts. Immunohistochemistry using the markers Ki-67 (proliferation), Cleave Caspase 3 (apoptosis), KRT20 (differentiation) were done in colon. IHC of retinoic acid binding proteins (anti-CRBP2 and anti-FABP5) were also performed Results: The experimental group had shown significantly higher total average intestinal tumor burden (6.8 fold) (p=0.0007) and total average tumor counts observed (3.6 fold) (p=0.02). In the colon, there was a 3.5-fold increase in average tumor burden (p=0.017) with a 2.7-fold increase in average tumor size (p=0.025)in the experimental group. We also noticed a trend of increased average tumor counts observed in the colon of the experimental group although statistically insignificant. Average tumor counts of ileum observed was 9-fold higher in experimental group with only 1 mice from control group showed observable small tumor growth which did not meet criteria for tumor size and tumor burden calculation. There were no significant differences in observable tumor counts, tumor size and tumor burden in jejunum. Histologically, all tumors were pedunculated adenocarcinomas. Many unobservable small tumors less than 1mm width and length were seen in the H&E of both ileum and jejunum in the experimental and control group. In the control group, there was less observable tumors compared to the experimental group although the tumor counts on H&E in both groups showed no major differences. This indicates that the tumor size in the experimental group was larger than the control group. On the contrary, average tumor counts of colon in H&E were lower compared to tumor counts observed in both control and experimental groups, indicating low number of small unobservable tumors in colon. Although the tumor counts of colon on H&E and observation between the two groups were statistically insignificant, we noticed a pattern of increased tumor counts in the experimental group suggesting a potential increase in tumor incidence. Immunohistochemical staining of colon is ongoing. Conclusion: ALDH1B1 reduced tumor growth rate in the ileum, and reduced tumor size in the colon suggesting its role in tumor promotion and progression. A larger number of experimental and control group is required to establish its potentially tumor-initiating role in the colon. Further characterization of ALDH1B1 in colon carcinogenesis is ongoing. We are also elucidating the role and regulation of retinoic acid signaling by ALDH1B1 in colorectal tumor growth. Citation Format: Wan Ying Tan, David. J. Orlicky, Ying Chen, Yatrik M. Shah, David C. Thompson, Vasilis Vasiliou. Role of aldehyde dehydrogenase 1B1 in colon carcinogenesis in a newly developed mouse model [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6141.