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The extracellular matrix protein EMILIN-1 impacts on the microenvironment by hampering gastric cancer development and progression.
- Source :
-
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association [Gastric Cancer] 2024 Sep; Vol. 27 (5), pp. 1016-1030. Date of Electronic Publication: 2024 Jun 28. - Publication Year :
- 2024
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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.<br />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.<br />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.<br />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.<br /> (© 2024. The Author(s).)
Details
- Language :
- English
- ISSN :
- 1436-3305
- Volume :
- 27
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
- Publication Type :
- Academic Journal
- Accession number :
- 38941035
- Full Text :
- https://doi.org/10.1007/s10120-024-01528-z