Pd14-02 Pathological Elucidation of Cellular Dynamics in Bladder Cancer Stroma Using a Three-Dimensional Collagen Model Reproducing Cancer-Specific Microenvironment

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology II (PD14)1 May 2024PD14-02 PATHOLOGICAL ELUCIDATION OF CELLULAR DYNAMICS IN BLADDER CANCER STROMA USING A THREE-DIMENSIONAL COLLAGEN MODEL REPRODUCING CANCER-SPECIFIC MICROENVIRONMENT Maki Kawasaki, Kei Nagase, Megumi Nishiyama, Kazuma Udo, Shohei Tobu, Shigehisa Aoki, and Mitsuru Noguchi Maki KawasakiMaki Kawasaki , Kei NagaseKei Nagase , Megumi NishiyamaMegumi Nishiyama , Kazuma UdoKazuma Udo , Shohei TobuShohei Tobu , Shigehisa AokiShigehisa Aoki , and Mitsuru NoguchiMitsuru Noguchi View All Author Informationhttps://doi.org/10.1097/01.JU.0001009472.76470.8c.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In developing cancer treatment strategies, the characterization of the cancer microenvironment is critical, as it influences the behavior and grade of cancer cells. This study utilized a novel three-dimensional collagen model to simulate key environmental factors affecting bladder cancer cell dynamics, focusing on (1) the individual impact of each microenvironment component, (2) the interplay between biological, physical, and chemical factors, and (3) the intra-component interactions. METHODS: Biological factors were represented by adipose tissue stromal cells (ATSCs), NIH3T3 fibroblast cells, and sections of adipose tissue, all embedded in a type I collagen gel matrix formed into discs. These discs served as substrates for bladder cancer cell lines, including NMIBC (non-muscle-invasive bladder cancer, RT4) and MIBC (muscle-invasive bladder cancer, T24), which were cultured atop the collagen constructs. Subsequent exposure to fluidic shear stress simulated the physical factor, while treatment with chemotherapeutic agents, such as cisplatin, constituted the chemical factor. Changes in cellular behavior were monitored histologically. Protein expression related to these behaviors was assessed through protein arrays and Western blotting techniques. RESULTS: Both biological (stromal cells) and physical (fluid shear stress) factors influenced the proliferative capacity and apoptotic rates of bladder cancer cells in a manner dependent on the cell line's invasive characteristics. Additionally, the sensitivity of bladder cancer cells to chemotherapy was modulated by these factors, impacting response to chemotactic agents like cisplatin. Differential expression of signaling proteins, namely ERK1/2 and p38, was observed across different invasion types, indicating variable response pathways. CONCLUSIONS: The study highlights the complex interdependency of factors within the cancer microenvironment that contribute to the regulation of cell proliferation, chemosensitivity, and protein expression patterns. A thorough understanding of the interrelated actions of these environmental components is crucial for the functional analysis of cancer behavior and tailoring microenvironment-specific therapeutic interventions. Download PPT Source of Funding: No funds available © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e353 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Maki Kawasaki More articles by this author Kei Nagase More articles by this author Megumi Nishiyama More articles by this author Kazuma Udo More articles by this author Shohei Tobu More articles by this author Shigehisa Aoki More articles by this author Mitsuru Noguchi More articles by this author Expand All Advertisement PDF downloadLoading ...