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Endocrinology. 2018 Jul 1;159(7):2656-2669. doi: 10.1210/en.2018-00151.

Proteomic Characterization of the Extracellular Matrix of Human Uterine Fibroids.

Author information

1
School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia.
2
School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia.
3
Department of Maternity and Gynecology, John Hunter Hospital, New Lambton Heights, New South Wales, Australia.

Abstract

Uterine leiomyomas (fibroids) are the most common benign tumors that are associated with increased production of extracellular matrix (ECM). Excessive ECM deposition plays a major role in the enlargement and stiffness of these tumors and contributes to clinical symptoms, such as abnormal bleeding and abdominal pain. However, no study so far has explored the global composition of the ECM of fibroids and normal myometrium. In this study, we performed a systematic ECM enrichment procedure and comparative proteomic analyses to profile the ECM composition of genetically annotated different-sized fibroids (small, medium, and large) and adjacent normal myometrium (ANM). Our matrisome analysis identified a combined total of 108, 126, 126, and 130 unique ECM and ECM-associated proteins with a confidence corresponding to a false discovery rate <1% in ANM and in small, medium, and large fibroids, respectively. The majority of fibroid ECM proteins belong to the core matrisome that includes glycoproteins, collagens, and proteoglycans. Considering that the small-sized fibroids represent the initial stages of leiomyogenesis, we highlighted some of the most abundant and important upregulated ECM proteins in small fibroids (i.e., POSTN, TNC, COL3A1, COL24A1, and ASPN). Furthermore, we revealed 30 unique ECM proteins that exist only in fibroids but that are not present in ANM regardless of MED12 mutation. We propose that some of the proteins identified represent potential novel ECM drug targets that may change the paradigm of fibroid treatment.

PMID:
29788081
DOI:
10.1210/en.2018-00151
[Indexed for MEDLINE]

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