دورية أكاديمية
COL6A3 Exosomes Promote Tumor Dissemination and Metastasis in Epithelial Ovarian Cancer.
العنوان: | COL6A3 Exosomes Promote Tumor Dissemination and Metastasis in Epithelial Ovarian Cancer. |
---|---|
المؤلفون: | Ho CM; Gynecologic Cancer Center, Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei 106, Taiwan.; School of Medicine, Fu Jen Catholic University, Hsinchuang, New Taipei City 242, Taiwan.; Department of Medical Research, Cathay General Hospital, Sijhih, New Taipei City 221, Taiwan., Yen TL; Department of Medical Research, Cathay General Hospital, Sijhih, New Taipei City 221, Taiwan.; School of Medicine, Taipei Medical University, Taipei 110, Taiwan., Chang TH; Graduate Institute of Biomedical Informatics, Taipei Medical University, Taipei 110, Taiwan., Huang SH; Department of Pathology, Cathay General Hospital, Taipei 106, Taiwan. |
المصدر: | International journal of molecular sciences [Int J Mol Sci] 2024 Jul 25; Vol. 25 (15). Date of Electronic Publication: 2024 Jul 25. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Basel, Switzerland : MDPI, [2000- |
مواضيع طبية MeSH: | Exosomes*/metabolism , Exosomes*/genetics , Carcinoma, Ovarian Epithelial*/pathology , Carcinoma, Ovarian Epithelial*/genetics , Carcinoma, Ovarian Epithelial*/metabolism , Collagen Type VI*/metabolism , Collagen Type VI*/genetics , Ovarian Neoplasms*/pathology , Ovarian Neoplasms*/genetics , Ovarian Neoplasms*/metabolism, Female ; Humans ; Animals ; Mice ; Cell Line, Tumor ; Neoplasm Metastasis ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Cell Movement |
مستخلص: | Our study explores the role of cancer-derived extracellular exosomes (EXs), particularly focusing on collagen alpha-3 (VI; COL6A3), in facilitating tumor dissemination and metastasis in epithelial ovarian cancer (EOC). We found that COL6A3 is expressed in aggressive ES2 derivatives, SKOV3 overexpressing COL6A3 (SKOV3/COL6A3), and mesenchymal-type ovarian carcinoma stromal progenitor cells (MSC-OCSPCs), as well as their EXs, but not in less aggressive SKOV3 cells or ES2 cells with COL6A3 knockdown (ES2/shCOL6A3). High COL6A3 expression correlates with worse overall survival among EOC patients, as evidenced by TCGA and GEO data analysis. In vitro experiments showed that EXs from MSC-OCSPCs or SKOV3/COL6A3 cells significantly enhance invasion ability in ES2 or SKOV3/COL6A3 cells, respectively (both, p <0.001). In contrast, ES2 cells with ES2/shCOL6A3 EXs exhibited reduced invasion ability ( p < 0.001). In vivo, the average disseminated tumor numbers in the peritoneal cavity were significantly greater in mice receiving intraperitoneally injected SKOV3/COL6A3 cells than in SKOV3 cells ( p < 0.001). Furthermore, mice intravenously (IV) injected with SKOV3/COL6A3 cells and SKOV3/COL6A3-EXs showed increased lung colonization compared to mice injected with SKOV3 cells and PBS ( p = 0.007) or SKOV3/COL6A3 cells and PBS ( p = 0.039). Knockdown of COL6A3 or treatment with EX inhibitor GW4869 or rapamycin-abolished COL6A3-EXs may suppress the aggressiveness of EOC. |
References: | Cancer Biol Ther. 2018 Aug 3;19(8):722-734. (PMID: 29580188) J Proteomics. 2013 Mar 27;80:171-82. (PMID: 23333927) Lab Chip. 2016 Feb 7;16(3):489-96. (PMID: 26645590) Nat Rev Cancer. 2006 May;6(5):392-401. (PMID: 16572188) J Transl Med. 2019 Sep 14;17(1):309. (PMID: 31521169) Nat Rev Cancer. 2013 Apr;13(4):273-82. (PMID: 23426401) Nat Med. 2012 Jun;18(6):883-91. (PMID: 22635005) Cells. 2020 Apr 02;9(4):. (PMID: 32252322) Gynecol Obstet (Sunnyvale). 2013 Apr 29;Suppl 4:3. (PMID: 24466501) Cancer Biomark. 2015;15(6):783-8. (PMID: 26406420) Sci Rep. 2020 May 26;10(1):8686. (PMID: 32457479) J Transl Med. 2015 Nov 23;13:367. (PMID: 26597084) Mol Cancer. 2022 Nov 1;21(1):207. (PMID: 36320056) Gynecol Oncol. 2011 Nov;123(2):379-86. (PMID: 21903249) Mol Cancer Res. 2016 Mar;14(3):287-95. (PMID: 26631572) J Cell Physiol. 2019 Dec;234(12):21796-21809. (PMID: 31273798) Drug Discov Today. 2021 Jul;26(7):1656-1668. (PMID: 33798648) Nat Commun. 2021 Jun 23;12(1):3904. (PMID: 34162871) CA Cancer J Clin. 2019 Jan;69(1):7-34. (PMID: 30620402) Curr Biol. 2016 Mar 21;26(6):755-65. (PMID: 26948875) Nat Commun. 2018 Dec 19;9(1):5395. (PMID: 30568162) Cancer Cell. 2014 Apr 14;25(4):501-15. (PMID: 24735924) Cancer Med. 2014 Oct;3(5):1136-45. (PMID: 25044252) Oncogene. 2020 Feb;39(7):1600-1616. (PMID: 31700155) Int J Mol Sci. 2020 Apr 08;21(7):. (PMID: 32276321) Annu Rev Pathol. 2009;4:287-313. (PMID: 18842102) Int J Cancer. 2020 Apr 15;146(8):2268-2280. (PMID: 31904865) Nat Commun. 2017 Mar 06;8:14470. (PMID: 28262727) Semin Cell Dev Biol. 2017 Jul;67:3-10. (PMID: 28077297) Cancer Cell. 2003 Apr;3(4):377-86. (PMID: 12726863) Am J Cancer Res. 2022 Apr 15;12(4):1686-1706. (PMID: 35530273) Cancer Lett. 2017 Oct 28;407:84-92. (PMID: 28807820) BMC Cancer. 2013 Nov 21;13:554. (PMID: 24261855) Am J Pathol. 2016 Apr;186(4):733-47. (PMID: 27012190) Biomark Cancer. 2011 Mar 03;3:15-23. (PMID: 24179387) Int J Clin Oncol. 2011 Oct;16(5):605-9. (PMID: 21243393) Sci Rep. 2016 Jul 28;6:30599. (PMID: 27465284) Nat Rev Cancer. 2016 Aug 23;16(9):582-98. (PMID: 27550820) Am J Cancer Res. 2021 Mar 01;11(3):668-690. (PMID: 33791147) Oncotarget. 2016 Mar 29;7(13):16923-35. (PMID: 26943577) BMC Cancer. 2009 Jul 20;9:244. (PMID: 19619303) Mol Cancer Res. 2017 Jan;15(1):78-92. (PMID: 27758876) Gynecol Oncol. 2018 Nov;151(2):257-263. (PMID: 30177462) J Biomed Sci. 2012 Feb 14;19:23. (PMID: 22330345) BMC Cancer. 2015 Oct 24;15:789. (PMID: 26497956) Elife. 2016 Feb 27;5:e10250. (PMID: 26920219) EMBO J. 2017 Feb 15;36(4):397-408. (PMID: 28096180) Front Oncol. 2013 Sep 25;3:256. (PMID: 24093089) Mol Cancer. 2021 Oct 27;20(1):140. (PMID: 34706732) Best Pract Res Clin Obstet Gynaecol. 2017 May;41:3-14. (PMID: 27743768) Trends Mol Med. 2013 Jul;19(7):410-7. (PMID: 23639582) Sci Adv. 2015 Dec 18;1(11):e1500603. (PMID: 26824057) |
معلومات مُعتمدة: | 107-2314-B-281-005-MY3, 111-2314-B-281-008-MY3 National Science and Technology Council, Taiwan |
فهرسة مساهمة: | Keywords: COL6A3; aggressiveness; epithelial ovarian cancer; exosome inhibitor; exosomes; metastasis |
المشرفين على المادة: | 0 (Collagen Type VI) 0 (COL6A3 protein, human) |
تواريخ الأحداث: | Date Created: 20240810 Date Completed: 20240810 Latest Revision: 20240812 |
رمز التحديث: | 20240813 |
مُعرف محوري في PubMed: | PMC11311469 |
DOI: | 10.3390/ijms25158121 |
PMID: | 39125689 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1422-0067 |
---|---|
DOI: | 10.3390/ijms25158121 |