Department of Anatomy, School of Medicine - FAMERP, Avenida Brigadeiro Faria Lima 5416, CEP 15090-000, São José do Rio Preto, SP, Brazil.
Cancer Cell Int. 2010 Jun 22;10:18. doi: 10.1186/1475-2867-10-18.
In this study the effect of myenteric denervation induced by benzalconium chloride (BAC) on distribution of fibrillar components of extracellular matrix (ECM) and inflammatory cells was investigated in gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Rats were divided in four experimental groups: non-denervated (I) and denervated stomach (II) without MNNG treatment; non-denervated (III) and denervated stomachs (IV) treated with MNNG. For histopathological, histochemical and stereological analysis, sections of gastric fragments were stained with Hematoxylin-Eosin, Picrosirius-Hematoxylin, Gomori reticulin, Weigert's Resorcin-Fuchsin, Toluidine Blue and Alcian-Blue/Safranin (AB-SAF).
BAC denervation causes an increase in the frequency of reticular and elastic fibers in the denervated (group II) compared to the non-denervated stomachs (group I). The treatment of the animals with MNNG induced the development of adenocarcinomas in non-denervated and denervated stomachs (groups III and IV, respectively) with a notable increase in the relative volume of the stroma, the frequency of reticular fibers and the inflammatory infiltrate that was more intense in group IV. An increase in the frequency of elastic fibers was observed in adenocarcinomas of denervated (group IV) compared to the non-denervated stomachs (group III) that showed degradation of these fibers. The development of lesions (groups III and IV) was also associated with an increase in the mast cell population, especially AB and AB-SAF positives, the latter mainly in the denervated group IV.
The results show a strong association in the morphological alteration of the ECM fibrillar components, the increased density of mast cells and the development of tumors induced by MNNG in the non-denervated rat stomach or denervated by BAC. This suggests that the study of extracellular and intracellular components of tumor microenvironment contributes to understanding of tumor biology by action of myenteric denervation.
本研究旨在探讨氯化苯扎铵(BAC)诱导的肌间神经丛去神经支配对 N-甲基-N'-硝基-N-亚硝基胍(MNNG)诱导的胃癌发生过程中细胞外基质(ECM)纤维状成分和炎症细胞分布的影响。大鼠分为四组:未去神经支配的(I 组)和去神经支配的胃(II 组)未行 MNNG 处理;未去神经支配的(III 组)和去神经支配的胃(IV 组)行 MNNG 处理。对胃组织切片进行苏木精-伊红、苦味酸-苏木精、Gomori 网状纤维、Weigert 复红、甲苯胺蓝和阿利新蓝/固绿(AB-SAF)染色,进行组织病理学、组织化学和体视学分析。
BAC 去神经支配导致去神经支配胃(II 组)中网状和弹性纤维的频率增加,与未去神经支配胃(I 组)相比。MNNG 处理动物后,未去神经支配和去神经支配的胃(III 组和 IV 组)分别发展为腺癌,间质的相对体积、网状纤维的频率和炎症浸润明显增加,且 IV 组更为显著。去神经支配胃(IV 组)腺癌中观察到弹性纤维频率增加,与未去神经支配胃(III 组)相比,后者显示纤维降解。病变(III 组和 IV 组)的发展也与肥大细胞数量的增加有关,特别是 AB 和 AB-SAF 阳性,后者主要在去神经支配的 IV 组中。
结果表明,在未去神经支配的大鼠胃或 BAC 去神经支配的胃中,MNNG 诱导的 ECM 纤维状成分形态改变、肥大细胞密度增加和肿瘤发生之间存在很强的相关性。这表明,研究肿瘤微环境的细胞外和细胞内成分有助于通过肌间神经丛去神经支配作用来理解肿瘤生物学。