Abstract
The study intends to investigate the regulation of syndecan-1 in human uterine leiomyoma cells. Human syndecan-1 levels were detected by Western blot in uterus leimyoma's tissue. The efficacy of syndecan-1 silencing on the cell proliferation, metalloproteinases and extracellular matrix were determined through Cell Counting Kit (CCK8) assay and Western blot assay, respectively. We compared the respective and combined effect of mifepristone and syndecan-1 on cell proliferation and the expression of metalloproteinases and extracellular matrix (ECM) in human uterine leiomyoma cells. The inhibitory effects of Syndecan-1 silencing on proliferation, ECM and Matrix Metalloproteinase (MMP) were observed in human uterine leiomyoma cells. Furthermore, syndecan-1 inhibition enhanced the effects of mifepristone against uterine leiomyoma cell proliferation. The expression of MMPs and ECM components in human uterine leiomyoma cells was decreased dramatically after syndecan-1 silencing, which was promoted after mifepristone treatment. Altogether, syndecan-1 silencing enhanced the efficacy of mifepristone on the uterine leiomyoma cell proliferation and ECM formation. Therefore, targeting syndecan-1 represents a novel therapeutic strategy to treat uterine leiomyoma.
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Barbareschi M, Maisonneuve P, Aldovini D, Cangi MG, Pecciarini L, Angelo Mauri F, Veronese S, Caffo O, Lucenti A, Palma PD, Galligioni E, Doglioni C (2003) High syndecan-1 expression in breast carcinoma is related to an aggressive phenotype and to poorer prognosis. Cancer 98:474–483
Bhowmick NA, Neilson EG, Moses HL (2004) Stromal fibroblasts in cancer initiation and progression. Nature 432:332–337
Cardozo ER, Foster R, Karmon AE, Lee AE, Gatune LW, Rueda BR, Styer AK (2018) MicroRNA 21a–5p overexpression impacts mediators of extracellular matrix formation in uterine leiomyoma. Reprod Biol Endocrinol 16:46
Choi DS, Kim JH, Ryu HS, Kim HC, Han JH, Lee JS, Min CK (2007) Syndecan-1, a key regulator of cell viability in endometrial cancer. Int J Cancer 121:741–750
Chuang TD, Khorram O (2019) Cross-talk between miR-29c and transforming growth factor-β3 is mediated by an epigenetic mechanism in leiomyoma. Fertil Steril 112:1180–1189
Conejo JR, Kleeff J, Koliopanos A, Matsuda K, Zhu ZW, Goecke H, Bicheng N, Zimmermann A, Korc M, Friess H, Büchler MW (2000) Syndecan-1 expression is up-regulated in pancreatic but not in other gastrointestinal cancers. Int J Cancer 88:12–20
Cui J, Jin S, Jin C, Jin Z (2020) Syndecan-1 regulates extracellular matrix expression in keloid fibroblasts via TGF-β1/Smad and MAPK signaling pathways. Life Sci 254:117326
Davies EJ, Blackhall FH, Shanks JH, David G, McGown AT, Swindell R, Slade RJ, Martin-Hirsch P, Gallagher JT, Jayson GC (2004) Distribution and clinical significance of heparan sulfate proteoglycans in ovarian cancer. Clin Cancer Res 10:5178–5186
Go K, Ishino T, Nakashimo Y, Miyahara N, Ookubo T, Takeno S, Hirakawa K (2010) Analysis of syndecan-1 and TGF-beta expression in the nasal mucosa and nasal polyps. Auris Nasus Larynx 37:427–435
Hayashida K, Johnston DR, Goldberger O, Park PW (2006) Syndecan-1 expression in epithelial cells is induced by transforming growth factor beta through a PKA-dependent pathway. J Biol Chem 281:24365–24374
Ibrahim SA, Yip GW, Stock C, Pan JW, Neubauer C, Poeter M, Pupjalis D, Koo CY, Kelsch R, Schule R, Rescher U, Kiesel L, Gotte M (2012) Targeting of syndecan-1 by microRNA miR-10b promotes breast cancer cell motility and invasiveness via a Rho-GTPase- and E-cadherin-dependent mechanism. Int J Cancer 131:E884–E896
Joseph DS, Malik M, Nurudeen S, Catherino WH (2010) Myometrial cells undergo fibrotic transformation under the influence of transforming growth factor beta-3. Fertil Steril 93:1500–1508
Kato M, Saunders S, Nguyen H, Bernfield M (1995) Loss of cell surface syndecan-1 causes epithelia to transform into anchorage-independent mesenchyme-like cells. Mol Biol Cell 6:559–576
Laughlin SK, Schroeder JC, Baird DD (2010) New directions in the epidemiology of uterine fibroids. Semin Reprod Med 28:204–217
Lewis TD, Malik M, Britten J, Parikh T, Cox J, Catherino WH (2019) Ulipristal acetate decreases active TGF-β3 and its canonical signaling in uterine leiomyoma via two novel mechanisms. Fertil Steril 111:806–815
Liakou E, Mavrogonatou E, Pratsinis H, Rizou S, Evangelou K, Panagiotou PN, Karamanos NK, Gorgoulis VG, Kletsas D (2016) Ionizing radiation-mediated premature senescence and paracrine interactions with cancer cells enhance the expression of syndecan 1 in human breast stromal fibroblasts: the role of TGF-β. Aging (Albany NY) 8:1650–1669
Liebersbach BF, Sanderson RD (1994) Expression of syndecan-1 inhibits cell invasion into type I collagen. J Biol Chem 269:20013–20019
Lin PH, Kung HL, Chen HY, Huang KC, Hsia SM (2019) Isoliquiritigenin suppresses E2-induced uterine leiomyoma growth through the modulation of cell death program and the repression of ECM accumulation. Cancers (Basel) 11:1131
Liu R, Shi P, Nie Z, Liang H, Zhou Z, Chen W, Chen H, Dong C, Yang R, Liu S, Chen C (2016) Mifepristone suppresses basal triple-negative breast cancer stem cells by down-regulating KLF5 expression. Theranostics 6:533–544
Maheux R, Guilloteau C, Lemay A, Bastide A, Fazekas AT (1985) Luteinizing hormone-releasing hormone agonist and uterine leiomyoma: a pilot study. Am J Obstet Gynecol 152:1034–1038
Manon-Jensen T, Itoh Y, Couchman JR (2010) Proteoglycans in health and disease: the multiple roles of syndecan shedding. Febs J 277:3876–3889
Patel A, Malik M, Britten J, Cox J, Catherino WH (2016) Mifepristone inhibits extracellular matrix formation in uterine leiomyoma. Fertil Steril 105:1102–1110
Regős E, Abdelfattah HH, Reszegi A, Szilák L, Werling K, Szabó G, Kiss A, Schaff Z, Kovalszky I, Baghy K (2018) Syndecan-1 inhibits early stages of liver fibrogenesis by interfering with TGFβ1 action and upregulating MMP14. Matrix Biol 68–69:474–489
Shen Q, Zou S, Sheng B, Zhao M, Sun LZ, Zhu X (2019) Mifepristone inhibits IGF-1 signaling pathway in the treatment of uterine leiomyomas. Drug Des Dev Ther 13:3161–3170
Worapamorn W, Tam SP, Li H, Haase HR, Bartold PM (2002) Cytokine regulation of syndecan-1 and -2 gene expression in human periodontal fibroblasts and osteoblasts. J Periodontal Res 37:273–278
Yoshida S, Ohara N, Xu Q, Chen W, Wang J, Nakabayashi K, Sasaki H, Morikawa A, Maruo T (2010) Cell-type specific actions of progesterone receptor modulators in the regulation of uterine leiomyoma growth. Semin Reprod Med 28:260–273
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Shen, X., Wang, X. The function role and synergic effect of syndecan-1 for mifepristone in uterine leiomyoma. Cytotechnology 73, 179–187 (2021). https://doi.org/10.1007/s10616-021-00455-6
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DOI: https://doi.org/10.1007/s10616-021-00455-6