1. The extracellular matrix protein EMILIN-1 impacts on the microenvironment by hampering gastric cancer development and progression.
- Author
-
Capuano, Alessandra, Vescovo, Maddalena, Canesi, Simone, Pivetta, Eliana, Doliana, Roberto, Nadin, Maria Grazia, Yamamoto, Masami, Tsukamoto, Tetsuya, Nomura, Sachiyo, Pilozzi, Emanuela, Palumbo, Antonio, Canzonieri, Vincenzo, Cannizzaro, Renato, Scanziani, Eugenio, Baldassarre, Gustavo, Mongiat, Maurizio, and Spessotto, Paola
- Subjects
TRANSGENIC mice ,EXTRACELLULAR matrix proteins ,ANIMAL models in research ,COLON cancer ,TUMOR microenvironment - Abstract
Background: The contribution of the tumor microenvironment and extracellular matrix to the aggressive biology of Gastric Cancer (GC) has been recently characterized; however, the role of EMILIN-1 in this context is unknown. EMILIN-1 is an essential structural element for the maintenance of lymphatic vessel (LV) integrity and displays anti-proliferative properties as demonstrated in skin and colon cancer. Given the key role of LVs in GC progression, the aim of this study was to investigate the role of EMILIN-1 in GC mouse models. Methods: We used the syngeneic YTN16 cells which were injected subcutaneously and intraperitoneally in genetically modified EMILIN-1 mice. In alternative, carcinogenesis was induced using N-Methyl-N-nitrosourea (MNU). Mouse-derived samples and human biopsies were analyzed by IHC and IF to the possible correlation between EMILIN-1 expression and LV pattern. Results: Transgenic mice developed tumors earlier compared to WT animals. 20 days post-injection tumors developed in EMILIN-1 mutant mice were larger and displayed a significant increase of lymphangiogenesis. Treatment of transgenic mice with MNU associated with an increased number of tumors, exacerbated aggressive lesions and higher levels of LV abnormalities. A significant correlation between the levels of EMILIN-1 and podoplanin was detected also in human samples, confirming the results obtained with the pre-clinical models. Conclusions: This study demonstrates for the first time that loss of EMILIN-1 in GC leads to lymphatic dysfunction and proliferative advantages that sustain tumorigenesis, and assess the use of our animal model as a valuable tool to verify the fate of GC upon loss of EMILIN-1. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF