Liot Sophie, Aubert Alexandre, Hervieu Valérie, Kholti Naïma El, Schalkwijk Joost, Verrier Bernard, Valcourt Ulrich, Lambert Elise
Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique (LBTI), UMR CNRS 5305, Université Lyon 1, Institut de Biologie et Chimie des Protéines, 7, passage du Vercors, F-69367 Lyon Cedex 07, France.
Service d'Anatomopathologie, Groupement Hospitalier Est, Hospices Civils de Lyon, Lyon, France.
Matrix Biol Plus. 2020 Jan 20;6-7:100021. doi: 10.1016/j.mbplus.2020.100021. eCollection 2020 May.
Cancer is a systemic disease involving multiple components produced from both tumor cells themselves and surrounding stromal cells. The pro- or anti-tumoral role of the stroma is still under debate. Indeed, it has long been considered the main physical barrier to the diffusion of chemotherapy by its dense and fibrous nature and its poor vascularization. However, in murine models, the depletion of fibroblasts, the main ExtraCellular Matrix (ECM)-producing cells, led to more aggressive tumors even though they were more susceptible to anti-angiogenic and immuno-modulators. Tenascin-C (TNC) is a multifunctional matricellular glycoprotein ( an ECM protein also able to induce signaling pathway) and is considered as a marker of tumor expansion and metastasis. However, the status of other tenascin (TN) family members and particularly Tenascin-X (TNX) has been far less studied during this pathological process and is still controversial. Herein, through (1) analyses of the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases and (2) immunohistochemistry staining of Tissue MicroArrays (TMA), we performed a large and extensive study of TNX expression at both mRNA and protein levels (1) in the 6 cancers with the highest incidence and mortality in the world ( lung, breast, colorectal, prostate, stomach and liver) and (2) in the cancers for which sparse data regarding TNX expression already exist in the literature. We thus demonstrated that, in most cancers, TNX expression is significantly downregulated during cancer progression and we also highlighted, when data were available, that high mRNA expression in cancer is correlated with a good survival prognosis.
癌症是一种全身性疾病，涉及肿瘤细胞自身以及周围基质细胞产生的多种成分。基质的促肿瘤或抗肿瘤作用仍存在争议。事实上，长期以来，由于其致密的纤维性质和较差的血管化，它一直被认为是化疗扩散的主要物理屏障。然而，在小鼠模型中，成纤维细胞（产生细胞外基质的主要细胞）的耗竭导致肿瘤更具侵袭性，尽管它们对抗血管生成和免疫调节剂更敏感。腱生蛋白-C（TNC）是一种多功能基质细胞糖蛋白（一种也能够诱导信号通路的细胞外基质蛋白），被认为是肿瘤扩展和转移的标志物。然而，在此病理过程中，其他腱生蛋白（TN）家族成员，特别是腱生蛋白-X（TNX）的情况研究得要少得多，并且仍然存在争议。在此，通过（1）对基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）数据库的分析，以及（2）组织微阵列（TMA）的免疫组织化学染色，我们对TNX在mRNA和蛋白质水平的表达进行了大规模、广泛的研究，（1）在世界上发病率和死亡率最高的6种癌症（肺癌、乳腺癌、结直肠癌、前列腺癌、胃癌和肝癌）中，以及（2）在文献中已有关于TNX表达的稀疏数据的癌症中。因此，我们证明，在大多数癌症中，TNX表达在癌症进展过程中显著下调，并且当有数据可用时，我们还强调，癌症中高mRNA表达与良好的生存预后相关。
