Our studies previously verified the model of DMH-induced carcinogenesis to study the barrier function of the colon, as well as TJ proteins that determine the barrier properties of the colon (Bekusova et al, 2018). Claudin-3 and -4 have been shown to play a significant role in the development of colorectal cancer (CRC) (Bekusova et al, 2021), and some cytokines elevated in CRC have a selective regulatory effect on the proximal and distal parts of the colon (Bekusova et al, 2022).
CRC is characterized by different patient survival, genesis and incidence of tumors depending on their location - in the proximal or distal part of the colon. Proximal tumors form de novo, usually metastasize, are less responsive to treatment, and form predominantly in adults. In adolescents and young adults, distal tumors predominate, which are formed from precancerous formations such as serrated adenomas that precede them, and their treatment is characterized by a more favorable prognosis. Studies by a number of authors indicate that in cancer of various localizations, in particular in CRC and endometrial cancer, claudin-3, -4 and -7 are increased (Li J., 2021). To clarify the role of claudins in the development of cancer of different localizations, it is necessary to conduct a detailed study of these TJ proteins in different parts of the colon. Collaboration with Professor H. Wang, a scientist from Huazhong University of Science and Technology, will allow us to combine data on СRC and endometrial cancer and clarify the role of claudins in the carcinogenesis of different organs. Joint work to study the molecular pathways of action of claudins and data on the effects of claudins on tumor drug resistance will allow us to determine possible strategies for influencing the molecular targets of claudins, which will contribute to the development of methods for treating tumors of different localizations.
To achieve this goal, the following tasks were agreed upon: 1. investigation the localization of claudins in cancer (colon cancer, endometrial cancer) using Western blot and PCR analysis (Russia, China), 2. exploring the the localization and associated intracellular signaling pathways of claudins in drug-resistant cell lines (Russia), 3. exploring the precise molecular mechanism of claudins and drug resistance at the molecular level (China), 4. propose strategies for targeting claudins molecular targets to intervene in drug resistance (Russia, China).
Cooperation with the Medical College of Huazhong University of Science and Technology, due to mutual interest and focus on solving common problems, will contribute to the intensification of scientific work, increasing the international visibility of our university, as well as scientific progress, cultural exchange and mutual learning. The results of the study can be included in the training courses “Biology of Aging”, “Evolutionary Physiology” for 3rd and 4th year undergraduate students at St. Petersburg State University (Associate Professor V.V. Bekusova).
Expected results.
Articles that will be published in international journals with high IF. Suggested article titles: "Involvement of the TJ-proteins in colorectal and gynecological carcinogenesis", "Impact of the TJ-proteins on tumor drug resistance, strategies for targeting molecular targets of claudins". Suggested scientific journals for publication: Cancer Biology and Medicine (SJR, IF 5.5), International Journal of Molecular science (WoS, IF 5.6). Results planned for publication in non-periodic publications Abstracts that will be sent to International and Russian conferences (XXVIII Russian Oncology Congress, 2024, IX All-Russian Conference on Molecular Oncology 2024; International Conference on Medical and Health Science (ICMHS), 2024-2025).
Based on the cooperation results, both sides will apply the NSCF Funding for international cooperation and the International Cooperation Fund of the Ministry of Science and Technology.