Altered organization of collagen fibers in the uninvolved human colon mucosa 10 cm and 20 cm away from the malignant tumor

Altered organization of collagen fibers in the uninvolved human colon mucosa 10 cm and 20 cm away from the malignant tumor
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距恶性肿瘤10 cm和20 cm处未受病灶人结肠粘膜胶原纤维组织改变

DOI:
10.1038/s41598-020-63368-y
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发表时间:
2020-04-14
期刊:
影响因子:
4.6
通讯作者:
Rabasovic, Mihailo D.
Rabasovic, Mihailo D.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Despotovic, Sanja Z.;Milkcvic, Dorde N.;Rabasovic, Mihailo D.

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胶原纤维的重塑在癌症发生和发展的每个阶段都有描述。胶原纤维的形态和组织的变化有助于形成有利于癌症进展和转移发展的微环境。然而,关于远离癌症的健康粘膜中胶原纤维重塑的数据很少。使用SHG成像,电子显微镜和专门的软件(CT-FIRE,CurveAlign和FiberFit),我们客观地可视化和量化胶原纤维的形态和组织的变化,并研究了与健康粘膜相比,距离癌症10 cm和20 cm的结肠粘膜中胶原重塑(合成,降解和胶原交联的变化)的可能原因。我们发现,在远离结肠癌的固有层中,胶原结构(胶原纤维和纤维内胶原分子的宽度、直线度、排列)发生变化,肌成纤维细胞的表达增加,胶原重塑酶(LOX和MMP 2)的表达增加。因此,已经在癌症微环境中描述的胶原纤维组织的变化也存在于远离癌症的粘膜中,但幅度较小。
Remodelling of collagen fibers has been described during every phase of cancer genesis and progression. Changes in morphology and organization of collagen fibers contribute to the formation of microenvironment that favors cancer progression and development of metastasis. However, there are only few data about remodelling of collagen fibers in healthy looking mucosa distant from the cancer. Using SHG imaging, electron microscopy and specialized softwares (CT-FIRE, CurveAlign and FiberFit), we objectively visualized and quantified changes in morphology and organization of collagen fibers and investigated possible causes of collagen remodelling (change in syntheses, degradation and collagen cross-linking) in the colon mucosa 10 cm and 20 cm away from the cancer in comparison with healthy mucosa. We showed that in the lamina propria this far from the colon cancer, there were changes in collagen architecture (width, straightness, alignment of collagen fibers and collagen molecules inside fibers), increased representation of myofibroblasts and increase expression of collagen-remodelling enzymes (LOX and MMP2). Thus, the changes in organization of collagen fibers, which were already described in the cancer microenvironment, also exist in the mucosa far from the cancer, but smaller in magnitude.