Renner et al_JHC_2021.pdf (2.16 MB)
Multi-modal Profiling of the Extracellular Matrix of Human Fallopian Tubes and Serous Tubal Intraepithelial Carcinomas
journal contributionposted on 2023-08-22, 21:22 authored by Carine Renner, Clarissa Gomez, Mike R Visetsouk, Isra Taha, Aisha Khan, Stephanie M McGregor, Paul Weisman, Alexandra NabaAlexandra Naba, Kristyn S Masters, Pamela K Kreeger
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. (J Histochem Cytochem XX: XXX-XXX, XXXX).
Acquisition of a Q-Exactive HF Mass Spectrometer | Funder: National Institutes of Health (Office of the Director) | Grant ID: S10OD027016
CitationRenner, C., Gomez, C., Visetsouk, M. R., Taha, I., Khan, A., McGregor, S. M., Weisman, P., Naba, A., Masters, K. S.Kreeger, P. K. (2022). Multi-modal Profiling of the Extracellular Matrix of Human Fallopian Tubes and Serous Tubal Intraepithelial Carcinomas. Journal of Histochemistry & Cytochemistry, 70(2), 151-168. https://doi.org/10.1369/00221554211061359
3101 Biochemistry and Cell Biology3404 Medicinal and Biomolecular Chemistry34 Chemical Sciences31 Biological SciencesOvarian CancerCancerBiotechnologyRare DiseasesCarcinoma, Ovarian EpithelialCystadenocarcinoma, SerousExtracellular MatrixFallopian TubesFemaleFibronectinsHumansMeta-Analysis as TopicOvarian NeoplasmsProteomicsVersicansmass spectrometrymatrisomemultispectral immunohistochemistrytumor microenvironmenttumor stroma06 Biological Sciences11 Medical and Health SciencesBiochemistry & Molecular Biology