Department of Biomedical Engineering (CR, MRV, AK, KSM, PKK) and Department of Materials Science & Engineering (KSM), University of Wisconsin-Madison, Madison, Wisconsin; Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, Illinois (CG, IT, AN).
University of Wisconsin Carbone Cancer Center (SMM, PW, KSM, PKK), Department of Pathology and Laboratory Medicine (SMM, PW), Department of Medicine (KSM), Department of Cell and Regenerative Biology (PKK), and Department of Obstetrics and Gynecology (PKK), University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; and University of Illinois Cancer Center, Chicago, Illinois (AN).
J Histochem Cytochem. 2022 Feb;70(2):151-168. doi: 10.1369/00221554211061359. Epub 2021 Dec 5.
Recent evidence supports the fimbriae of the fallopian tube as one origin site for high-grade serous ovarian cancer (HGSOC). The progression of many solid tumors is accompanied by changes in the microenvironment, including alterations of the extracellular matrix (ECM). Therefore, we sought to determine the ECM composition of the benign fallopian tube and changes associated with serous tubal intraepithelial carcinomas (STICs), precursors of HGSOC. The ECM composition of benign human fallopian tube was first defined from a meta-analysis of published proteomic datasets that identified 190 ECM proteins. We then conducted de novo proteomics using ECM enrichment and identified 88 proteins, 7 of which were not identified in prior studies (COL2A1, COL4A5, COL16A1, elastin, LAMA5, annexin A2, and PAI1). To enable future in vitro studies, we investigated the levels and localization of ECM components included in tissue-engineered models (type I, III, and IV collagens, fibronectin, laminin, versican, perlecan, and hyaluronic acid) using multispectral immunohistochemical staining of fimbriae from patients with benign conditions or STICs. Quantification revealed an increase in stromal fibronectin and a decrease in epithelial versican in STICs. Our results provide an in-depth picture of the ECM in the benign fallopian tube and identified ECM changes that accompany STIC formation. .
最近的证据支持输卵管纤毛是高级别浆液性卵巢癌（HGSOC）的一个起源部位。许多实体瘤的进展伴随着微环境的变化，包括细胞外基质（ECM）的改变。因此，我们试图确定良性输卵管的 ECM 组成以及与浆液性输卵管上皮内癌（STIC）相关的变化，STIC 是 HGSOC 的前体。首先，我们通过对已发表的蛋白质组学数据集进行荟萃分析，确定了 190 种 ECM 蛋白，从而定义了良性人输卵管的 ECM 组成。然后，我们使用 ECM 富集进行了从头蛋白质组学研究，鉴定出 88 种蛋白质，其中 7 种在先前的研究中未被鉴定出（COL2A1、COL4A5、COL16A1、弹性蛋白、LAMA5、膜联蛋白 A2 和 PAI1）。为了能够进行未来的体外研究，我们使用多光谱免疫组织化学染色法对来自良性疾病或 STIC 患者的输卵管纤毛进行了组织工程模型（I 型、III 型和 IV 型胶原蛋白、纤维连接蛋白、层粘连蛋白、软骨素聚糖、基膜聚糖、透明质酸）中包含的 ECM 成分的水平和定位进行了研究。定量分析显示 STIC 中基质纤维连接蛋白增加，上皮软骨素聚糖减少。我们的研究结果提供了良性输卵管中 ECM 的详细图片，并确定了伴随 STIC 形成的 ECM 变化。
