Abstract 1988: Association Between CEACAMs and Hypoxia Defines Gastric Cancer Progression

Abstract Background: Gastric cancer is one of the most prevalent cancers. As in many other solid tumors, hypoxia is a notable feature in gastric cancer as well. The hypoxic microenvironment promotes cancer by modulating expression of several master regulator oncoproteins. Carcinoembryonic antigen-related cell adhesion molecules or (CEACAMs) are adhesion proteins that have been associated with many epithelial tumors but their expression pattern in hypoxic gastric epithelial cells are not known. Since these membrane proteins have widespread roles in the intracellular and intercellular signaling, inflammation, angiogenesis and metastasis, we examined hypoxia-mediated regulation of CEACAM proteins. Methods: AGS, MKN45 and primary gastric epithelial cells were subjected to hypoxia of varying degrees and the changes in the CEACAM protein profile were evaluated by immunoblotting, FACS assay and immunofluorescence microscopy. In vitro DNA-binding assay and luciferase assays were performed to assess the transcriptional regulation of CEACAMs. Overexpression and suppression studies were also performed to elucidate upstream regulations of CEACAM proteins. Gastric cancer biopsy tissues were examined from consenting patients by performing fluorescence and confocal microscopy. Results: We found that varying degrees of hypoxia differentially modulate CEACAM expression in gastric cancer epithelial cells which in turn leads to altered proliferation and invasiveness of cancer cells. Interestingly, gastric adenocarcinoma and metastatic gastric cancer biopsies show distinct CEACAM signatures. These findings unfold further avenues highlighting the importance of CEACAM proteins as biomarkers of gastric cancer and as therapeutic targets to treat gastric cancer. Funding: Department of Atomic Energy (DAE). Citation Format: Indrajit Poirah, Debashish Chakraborty, Pragyesh Dixit, Supriya Samal, Pratyush Kumar Padhan, Alok Barik, Shivaram Prasad Singh, Bernhard B. Singer, Asima Bhattacharyya. Association between CEACAMs and hypoxia defines gastric cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1988.