Rusu Stefan, Nuyens Vincent, Rousseau Alexandre, Lothaire Philippe, Nagy Nathalie, Boudjeltia Karim Zouaoui, Uzureau Pierrick
Department of Pathology, Hôpital Universitaire de Bruxelles, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
Centre Universitaire Inter Régional d'Expertise en Anatomie Pathologique Hospitalière, Charleroi, Belgium.
Histol Histopathol. 2024 Dec 3:18858. doi: 10.14670/HH-18-858.
Due to the late-stage diagnosis of head and neck squamous cell carcinoma (HNSCC), treatment remains a significant clinical challenge. The metalloproteinases MMP-9 and MT1-MMP play a pivotal role in extracellular matrix remodeling, thereby facilitating tumor growth and metastasis. Tumor progression requires the degradation of the basement membrane. The principal components of this structure, namely collagen IV and laminin, are the main targets of both MMP-9 and MT1-MMP. However, they can also exert influence over the expression of these enzymes. Oxidative stress plays an instrumental role in tumor development, functioning as a key inducer of metalloproteinase expression. The present study investigates the distribution of MMP-9 and MT1-MMP within tumor nests and along the basement membrane, comparing these with the distributions of collagen IV, laminin-332, and the antioxidant MnSOD. Biopsies from 12 patients with HNSCC and poor prognostic factors were subjected to immunofluorescence analysis. MMP-9 and MT1-MMP were found to be predominantly present in tumor cells, with a significant decrease in expression from the periphery to the center of tumor nests. Co-localization studies with laminin-332 and collagen IV, revealed substantial overlap, in accordance with the role of MMPs in basal membrane degradation. The cellular expression of laminin-332 associated with MMP-9 expression suggests an intricate relationship between metalloproteinases and their targets. While the previously observed pattern of glutathione-producing enzyme was similar to the metalloproteinases pattern, MnSOD expression was homogeneously distributed within tumor nests. Our findings reveal various distribution patterns of oxidative stress regulators, suggesting a complicated interplay in the development of HNSCC.
由于头颈部鳞状细胞癌（HNSCC）的晚期诊断，治疗仍然是一项重大的临床挑战。金属蛋白酶MMP-9和MT1-MMP在细胞外基质重塑中起关键作用，从而促进肿瘤生长和转移。肿瘤进展需要基底膜的降解。这种结构的主要成分，即IV型胶原蛋白和层粘连蛋白，是MMP-9和MT1-MMP的主要靶点。然而，它们也可以对这些酶的表达产生影响。氧化应激在肿瘤发展中起重要作用，是金属蛋白酶表达的关键诱导剂。本研究调查了MMP-9和MT1-MMP在肿瘤巢内和沿基底膜的分布，并将其与IV型胶原蛋白、层粘连蛋白-332和抗氧化剂MnSOD的分布进行比较。对12例具有不良预后因素的HNSCC患者的活检组织进行免疫荧光分析。发现MMP-9和MT1-MMP主要存在于肿瘤细胞中，从肿瘤巢的周边到中心表达显著降低。与层粘连蛋白-332和IV型胶原蛋白的共定位研究显示有大量重叠，这与MMPs在基底膜降解中的作用一致。与MMP-9表达相关的层粘连蛋白-332的细胞表达表明金属蛋白酶与其靶点之间存在复杂的关系。虽然先前观察到的产生谷胱甘肽的酶的模式与金属蛋白酶的模式相似，但MnSOD表达在肿瘤巢内均匀分布。我们的研究结果揭示了氧化应激调节因子的各种分布模式，表明在HNSCC的发展中存在复杂的相互作用。
