细胞外基质蛋白EMILIN-1通过阻碍胃癌的发生和发展对微环境产生影响。

IF 6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Gastric Cancer Pub Date : 2024-09-01 Epub Date: 2024-06-28 DOI:10.1007/s10120-024-01528-z
Alessandra Capuano, Maddalena Vescovo, Simone Canesi, Eliana Pivetta, Roberto Doliana, Maria Grazia Nadin, Masami Yamamoto, Tetsuya Tsukamoto, Sachiyo Nomura, Emanuela Pilozzi, Antonio Palumbo, Vincenzo Canzonieri, Renato Cannizzaro, Eugenio Scanziani, Gustavo Baldassarre, Maurizio Mongiat, Paola Spessotto
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引用次数: 0

摘要

背景:肿瘤微环境和细胞外基质对胃癌(GC)侵袭性生物学特性的贡献最近已得到证实;然而,EMILIN-1在其中的作用尚不清楚。EMILIN-1 是维持淋巴管(LV)完整性的重要结构元素,在皮肤癌和结肠癌中表现出抗增殖特性。鉴于淋巴管在 GC 进展中的关键作用,本研究旨在探讨 EMILIN-1 在 GC 小鼠模型中的作用:方法:我们使用合成 YTN16 细胞,将其皮下注射和腹腔注射到转基因 EMILIN-1 小鼠体内。另一种方法是使用 N-甲基-N-亚硝基脲(MNU)诱导癌变。通过 IHC 和 IF 分析小鼠样本和人类活组织切片,研究 EMILIN-1 表达与 LV 模式之间可能存在的相关性:结果:与 WT 动物相比,转基因小鼠更早出现肿瘤。注射后20天,EMILIN-1突变体小鼠的肿瘤更大,淋巴管生成显著增加。用 MNU 治疗转基因小鼠会导致肿瘤数量增加、侵袭性病变加剧和 LV 异常水平升高。在人体样本中也检测到了EMILIN-1和podoplanin水平之间的明显相关性,证实了临床前模型获得的结果:本研究首次证明了在GC中EMILIN-1的缺失会导致淋巴功能障碍和增殖优势,从而维持肿瘤发生,并评估了我们的动物模型作为一种有价值的工具,可用于验证EMILIN-1缺失后GC的命运。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The extracellular matrix protein EMILIN-1 impacts on the microenvironment by hampering gastric cancer development and progression.

The extracellular matrix protein EMILIN-1 impacts on the microenvironment by hampering gastric cancer development and progression.

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.

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来源期刊
Gastric Cancer
Gastric Cancer 医学-胃肠肝病学
CiteScore
14.70
自引率
2.70%
发文量
80
审稿时长
6-12 weeks
期刊介绍: Gastric Cancer is an esteemed global forum that focuses on various aspects of gastric cancer research, treatment, and biology worldwide. The journal promotes a diverse range of content, including original articles, case reports, short communications, and technical notes. It also welcomes Letters to the Editor discussing published articles or sharing viewpoints on gastric cancer topics. Review articles are predominantly sought after by the Editor, ensuring comprehensive coverage of the field. With a dedicated and knowledgeable editorial team, the journal is committed to providing exceptional support and ensuring high levels of author satisfaction. In fact, over 90% of published authors have expressed their intent to publish again in our esteemed journal.
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