成纤维细胞源性基质通过模拟细胞间质性质，在癌症进展中形成一个预后标志。
Fibroblast-derived matrix models desmoplastic properties and forms a prognostic signature in cancer progression.
发表日期：2023
作者：
Maria Rafaeva, Adina R D Jensen, Edward R Horton, Kamilla W Zornhagen, Jan E Strøbech, Lutz Fleischhauer, Alejandro E Mayorca-Guiliani, Sebastian R Nielsen, Dina S Grønseth, Filip Kuś, Erwin M Schoof, Luis Arnes, Manuel Koch, Hauke Clausen-Schaumann, Valerio Izzi, Raphael Reuten, Janine T Erler
来源：
BIOMEDICINE & PHARMACOTHERAPY
摘要：
许多癌症中观察到的致密反应是疾病进展和预后的标志，尤其是在乳腺癌和胰腺癌中。基质来源的细胞外基质（ECM）在致密反应中发生了显著改变，因此在推动癌症进展中起着关键作用。我们利用成纤维细胞衍生的基质（FDMs）展示了癌细胞在与癌相关的FDMs上的增长明显高于从非恶性组织（正常）成纤维细胞衍生的FDMs。我们评估了原发肿瘤部位从正常到癌相关的基质的ECM特性的变化。组成、结构和力学分析显示出显著差异，癌相关的FDMs中的核心ECM蛋白丰度增加，同时硬度和密度也增加。通过对FDM的组成变化，我们得到了一个由36个ECM蛋白签名，我们展示这个签名在胰导管腺癌（PDAC）肿瘤和转移的进展中大部分与之匹配。此外，这个签名在多种癌症类型的患者中的转录组水平也匹配，与其生存期相关。综上所述，我们的结果显示FDM对于癌症建模和鉴定致密ECM组分的相关性，进而进行进一步的机制研究。Copyright © 2023 Rafaeva, Jensen, Horton, Zornhagen, Strøbech, Fleischhauer, Mayorca-Guiliani, Nielsen, Grønseth, Kuś, Schoof, Arnes, Koch, Clausen-Schaumann, Izzi, Reuten and Erler.
The desmoplastic reaction observed in many cancers is a hallmark of disease progression and prognosis, particularly in breast and pancreatic cancer. Stromal-derived extracellular matrix (ECM) is significantly altered in desmoplasia, and as such plays a critical role in driving cancer progression. Using fibroblast-derived matrices (FDMs), we show that cancer cells have increased growth on cancer associated FDMs, when compared to FDMs derived from non-malignant tissue (normal) fibroblasts. We assess the changes in ECM characteristics from normal to cancer-associated stroma at the primary tumor site. Compositional, structural, and mechanical analyses reveal significant differences, with an increase in abundance of core ECM proteins, coupled with an increase in stiffness and density in cancer-associated FDMs. From compositional changes of FDM, we derived a 36-ECM protein signature, which we show matches in large part with the changes in pancreatic ductal adenocarcinoma (PDAC) tumor and metastases progression. Additionally, this signature also matches at the transcriptomic level in multiple cancer types in patients, prognostic of their survival. Together, our results show relevance of FDMs for cancer modelling and identification of desmoplastic ECM components for further mechanistic studies.Copyright © 2023 Rafaeva, Jensen, Horton, Zornhagen, Strøbech, Fleischhauer, Mayorca-Guiliani, Nielsen, Grønseth, Kuś, Schoof, Arnes, Koch, Clausen-Schaumann, Izzi, Reuten and Erler.