School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, West Bengal 721302, India.
School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, West Bengal 721302, India.
Eur J Cell Biol. 2021 Jan;100(1):151146. doi: 10.1016/j.ejcb.2020.151146. Epub 2020 Dec 23.
Oral sub-mucous fibrosis (OSF) is a pathophysiological state of oral cavity or oropharynx having a high chance of conversion to oral squamous cell carcinoma (OSCC). It involves fibrotic transformation of sub-epithelial matrix along with epithelial abnormalities. The present work aims to unveil the mechanistic domain regarding OSF to OSCC conversion exploring the scenario of hypoxia associated oxidative stress, epithelial-mesenchymal transition (EMT), metastasis and stemness acquisition. The study involves histopathological analysis of the diseased condition along with the exploration of oxidative stress status, assessment of mitochondrial condition, immunohistochemical analysis of HIF-1α, E-cadherin, vimentin, ERK, ALDH-1, CD133, Shh, Gli-1 and survivin expressions in the oral epithelial region together with the quantitative approach towards collagen deposition in the sub-epithelial matrix. Oxidative stress was found to be associated with type-II EMT in case of OSF attributing the development of sub-epithelial fibrosis and type-III EMT in case of OSCC favoring malignancy associated metastasis. Moreover, the acquisition of stemness during OSCC can also be correlated with EMT. Alteration of Shh and Gli-1 expression pattern revealed the mechanistic association of hypoxia with the phenotypic plasticity and disease manifestation in case of OSF as well as OSCC. Shh/ Gli-1 signaling can also be correlated with survivin mediated cytoprotective phenomenon under oxidative stress. Overall, the study established the correlative network of hypoxia associated oxidative stress, EMT and manifestation of oral pre-cancerous and cancerous condition in a holistic approach that may throw rays of hope in the therapeutic domain of the concerned diseases.
口腔黏膜下纤维性变（OSF）是一种口腔或口咽的病理生理状态，有很高的转化为口腔鳞状细胞癌（OSCC）的可能性。它涉及到上皮下基质的纤维化转化以及上皮异常。本工作旨在揭示 OSF 向 OSCC 转化的机制领域，探索与缺氧相关的氧化应激、上皮-间充质转化（EMT）、转移和获得干性的情况。该研究包括对疾病状况进行组织病理学分析，同时探索氧化应激状态，评估线粒体状况，免疫组织化学分析 HIF-1α、E-钙粘蛋白、波形蛋白、ERK、ALDH-1、CD133、Shh、Gli-1 和 survivin 在口腔上皮区域的表达，以及对上皮下基质中胶原蛋白沉积进行定量分析。研究发现，在 OSF 中，氧化应激与 II 型 EMT 相关，导致了上皮下纤维化的发展，而在 OSCC 中，氧化应激与 III 型 EMT 相关，有利于恶性转移。此外，在 OSCC 中获得干性也可以与 EMT 相关。Shh 和 Gli-1 表达模式的改变揭示了缺氧与 OSF 以及 OSCC 中表型可塑性和疾病表现的机制关联。Shh/Gli-1 信号也可以与氧化应激下 survivin 介导的细胞保护现象相关。总的来说，该研究以整体的方式建立了缺氧相关氧化应激、EMT 以及口腔癌前病变和癌症表现的相关性网络，这可能为相关疾病的治疗领域带来希望。
