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Journal of Ovarian Research
Published in: Journal of Ovarian Research 1/2018

Open Access 01-12-2018 | Research

Cross-linked hyaluronan gel inhibits the growth and metastasis of ovarian carcinoma

Published in: Journal of Ovarian Research | Issue 1/2018

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Abstract

Background

The recurrence, metastasis and poor prognosis are important characteristics of ovarian carcinoma (OC), which are associated with exfoliation of cells from the primary tumor and colonization of the cells in pelvic cavity. On the other hand, the life quality of the patients undergoing surgical resection of OC was influenced by postoperative adhesions. Therefore, preventing postoperative implant tumor and adhesion may be effective methods to improve OC treatment. HyaRegen Gel, a cross-linked hyaluronan gel (CHAG), has been widely used as an anti-adhesive agent following pelvic operation in clinic. However, whether it can affect the implantation and growth of OC cells or not is still not clear.

Methods

Migration and invasion assays were applied to detect the effect of CHAG on migration and invasion of OC cells. Western blotting was performed to detect the phosphorylation/activation of EGFR and ERK, and the expression of PCNA and MMP7. Pull down assay was used to analyze the effect of CHAG on the activation of small G protein Rac1. Nude mice implantation tumor model was applied to observe the effect of CHAG on implantation tumor of OC cells.

Results

The results of in vitro experiments showed that CHAG suppressed both basic and EGF-induced migration and invasion of OC cells, blocked the activation of EGF-initiated EGFR activation, inhibited downstream signal transduction of EGFR, and decreased expression of proliferation and migration/invasion related proteins. Meanwhile, results of in vivo experiments showed that CHAG not only inhibited the formation of implantation tumor of OC cells but also delayed the of the growth of the tumors.

Conclusions

CHAG inhibited migration, invasion and proliferation of OC cells in vitro, and suppressed development of implantation tumor of OC in vivo. This made it as both anti-tumor and anti-adhesion agents.
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Literature
1.
Natanzon Y, Goode EL, Cunningham JM. Epigenetics in ovarian cancer. Semin cancer biol 2017.
2.
Montagnana M, Benati M, Danese E. Circulating biomarkers in epithelial ovarian cancer diagnosis: from present to future perspective. Ann Transl Med. 2017;5:276.CrossRefPubMedPubMedCentral
3.
Liu MM, Li PL. Clinical value of anti-adhesion agents used in laparotomy in obstetrics and gynecology. Zhonghua Fu Chan Ke Za Zhi. 2012;47:255–8.PubMed
4.
Papanikolaou G, Fotopoulou C, Braicu I, Chekerov R, Schmidt SC, Pietzner K, Sehouli J. First surgical experience of intraperitoneal treatment with the trifunctional antibody catumaxomab (anti-EpCam x anti-CD3) for epithelial ovarian cancer. Anticancer Res. 2011;31:2603–8.PubMed
5.
Fortin CN, Saed GM, Diamond MP. Predisposing factors to post-operative adhesion development. Hum Reprod Update. 2015;21:536–51.CrossRefPubMed
6.
Imudia AN, Kumar S, Saed GM, Diamond MP. Pathogenesis of intra-abdominal and pelvic adhesion development. Semin Reprod Med. 2008;26:289–97.CrossRefPubMed
7.
8.
Romano CL, De Vecchi E, Bortolin M, Morelli I, Drago L. Hyaluronic acid and its composites as a local antimicrobial/antiadhesive barrier. J Bone Jt Infect. 2017;2:63–72.CrossRefPubMedPubMedCentral
9.
10.
Naor D, Sionov RV, Ish-Shalom D. CD44: structure, function, and association with the malignant process. Adv Cancer Res. 1997;71:241–319.CrossRefPubMed
11.
Chen CH, Chen SH, Mao SH, Tsai MJ, Chou PY, Liao CH, Chen JP. Injectable thermosensitive hydrogel containing hyaluronic acid and chitosan as a barrier for prevention of postoperative peritoneal adhesion. Carbohydr Polym. 2017;173:721–31.CrossRefPubMed
12.
Liu C, Lu Q, Zhang Z, Xue M, Zhang Y, Wang H, Li H, Zhou Y, Li W. A randomized controlled trial on the efficacy and safety of a new crosslinked Hyaluronan gel in reducing adhesions after gynecologic laparoscopic surgeries. J Minim Invasive Gynecol. 2015;22:853–63.CrossRefPubMed
13.
Xiao S, Wan Y, Zou F, Ye M, Deng H, Ma J, Wei Y, Tan C, Xue M. Prevention of intrauterine adhesion with auto-crosslinked hyaluronic acid gel: a prospective, randomized, controlled clinical study. Zhonghua Fu Chan Ke Za Zhi. 2015;50:32–6.PubMed
14.
Lan T, Pang J, Wu Y, Zhu M, Yao X, Wu M, Qian H, Zhang Z, Gao J, Chen Y. Cross-linked hyaluronic acid gel inhibits metastasis and growth of gastric and hepatic cancer cells: in vitro and in vivo studies. Oncotarget. 2016;7:65418–28.PubMedPubMedCentral
15.
Gui T, Shen K. The epidermal growth factor receptor as a therapeutic target in epithelial ovarian cancer. Cancer Epidemiol. 2012;36:490–6.CrossRefPubMed
16.
Niikura H, Sasano H, Sato S, Yajima A. Expression of epidermal growth factor-related proteins and epidermal growth factor receptor in common epithelial ovarian tumors. Int J Gynecol Pathol. 1997;16:60–8.CrossRefPubMed
17.
Mehner C, Oberg AL, Kalli KR, Nassar A, Hockla A, Pendlebury D, Cichon MA, Goergen KM, Maurer MJ, Goode EL, et al. Serine protease inhibitor Kazal type 1 (SPINK1) drives proliferation and anoikis resistance in a subset of ovarian cancers. Oncotarget. 2015;6:35737–54.CrossRefPubMedPubMedCentral
18.
Psyrri A, Kassar M, Yu Z, Bamias A, Weinberger PM, Markakis S, Kowalski D, Camp RL, Rimm DL, Dimopoulos MA. Effect of epidermal growth factor receptor expression level on survival in patients with epithelial ovarian cancer. Clin Cancer Res. 2005;11:8637–43.CrossRefPubMed
19.
Lassus H, Sihto H, Leminen A, Joensuu H, Isola J, Nupponen NN, Butzow R. Gene amplification, mutation, and protein expression of EGFR and mutations of ERBB2 in serous ovarian carcinoma. J Mol Med (Berl). 2006;84:671–81.CrossRef
20.
Mehner C, Oberg AL, Goergen KM, Kalli KR, Maurer MJ, Nassar A, Goode EL, Keeney GL, Jatoi A, Radisky DC, Radisky ES. EGFR as a prognostic biomarker and therapeutic target in ovarian cancer: evaluation of patient cohort and literature review. Genes Cancer. 2017;8:589–99.PubMedPubMedCentral
21.
Wilken JA, Badri T, Cross S, Raji R, Santin AD, Schwartz P, Branscum AJ, Baron AT, Sakhitab AI, Maihle NJ. EGFR/HER-targeted therapeutics in ovarian cancer. Future Med Chem. 2012;4:447–69.CrossRefPubMedPubMedCentral
22.
Siwak DR, Carey M, Hennessy BT, Nguyen CT, McGahren Murray MJ, Nolden L, Mills GB. Targeting the epidermal growth factor receptor in epithelial ovarian cancer: current knowledge and future challenges. J Oncol. 2010;2010:568938.CrossRefPubMed
23.
Murphy M, Stordal B. Erlotinib or gefitinib for the treatment of relapsed platinum pretreated non-small cell lung cancer and ovarian cancer: a systematic review. Drug Resist Updat. 2011;14:177–90.CrossRefPubMed
24.
Donnelly SK, Bravo-Cordero JJ, Hodgson L. Rho GTPase isoforms in cell motility: Don’t FRET, we have FRET. Cell Adhes Migr. 2014;8:526–34.CrossRef
25.
Miyamoto Y, Suyama K, Baba H. Recent advances in targeting the EGFR signaling pathway for the treatment of metastatic colorectal cancer. Int J Mol Sci. 2017;18:752.
26.
Wertheimer E, Gutierrez-Uzquiza A, Rosemblit C, Lopez-Haber C, Sosa MS, Kazanietz MG. Rac signaling in breast cancer: a tale of GEFs and GAPs. Cell Signal. 2012;24:353–62.CrossRefPubMed
27.
Umelo IA, Wever OD, Kronenberger P, Noor A, Teugels E, Chen G, Bracke M, Greve JD. Combined inhibition of rho-associated protein kinase and EGFR suppresses the invasive phenotype in EGFR-dependent lung cancer cells. Lung Cancer. 2015;90:167–74.CrossRefPubMed
28.
Jurikova M, Danihel L, Polak S, Varga I. Ki67, PCNA, and MCM proteins: markers of proliferation in the diagnosis of breast cancer. Acta Histochem. 2016;118:544–52.CrossRefPubMed
29.
Shiomi T, Okada Y. MT1-MMP and MMP-7 in invasion and metastasis of human cancers. Cancer Metastasis Rev. 2003;22:145–52.CrossRefPubMed
30.
Martin Lluesma S, Wolfer A, Harari A, Kandalaft LE. Cancer vaccines in ovarian cancer: how can we improve? Biomedicine. 2016;4:10.
31.
Mais V, Angioli R, Coccia E, Fagotti A, Landi S, Melis GB, Pellicano M, Scambia G, Zupi E, Angioni S, et al. Prevention of postoperative abdominal adhesions in gynecological surgery. Consensus paper of an Italian gynecologists’ task force on adhesions. Minerva Ginecol. 2011;63:47–70.PubMed
32.
Pados G, Venetis CA, Almaloglou K, Tarlatzis BC. Prevention of intra-peritoneal adhesions in gynaecological surgery: theory and evidence. Reprod BioMed Online. 2010;21:290–303.CrossRefPubMed
33.
Johns DB, Keyport GM, Hoehler F, di Zerega GS. Reduction of postsurgical adhesions with Intergel adhesion prevention solution: a multicenter study of safety and efficacy after conservative gynecologic surgery. Fertil Steril. 2001;76:595–604.CrossRefPubMed
34.
Arslan E, Talih T, Oz B, Halaclar B, Caglayan K, Sipahi M. Comparison of lovastatin and hyaluronic acid/carboxymethyl cellulose on experimental created peritoneal adhesion model in rats. Int J Surg. 2014;12:120–4.CrossRefPubMed
35.
Wolny PM, Banerji S, Gounou C, Brisson AR, Day AJ, Jackson DG, Richter RP. Analysis of CD44-hyaluronan interactions in an artificial membrane system: insights into the distinct binding properties of high and low molecular weight hyaluronan. J Biol Chem. 2010;285:30170–80.CrossRefPubMedPubMedCentral
36.
Lafky JM, Wilken JA, Baron AT, Maihle NJ. Clinical implications of the ErbB/epidermal growth factor (EGF) receptor family and its ligands in ovarian cancer. Biochim Biophys Acta. 2008;1785:232–65.PubMed
37.
Mendelsohn J, Baselga J. The EGF receptor family as targets for cancer therapy. Oncogene. 2000;19:6550–65.CrossRefPubMed
38.
Normanno N, De Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR, Carotenuto A, De Feo G, Caponigro F, Salomon DS. Epidermal growth factor receptor (EGFR) signaling in cancer. Gene. 2006;366:2–16.CrossRefPubMed
39.
Wang C, Wang W, Liu Y, Yong M, Yang Y, Zhou H. Rac GTPase activating protein 1 promotes oncogenic progression of epithelial ovarian cancer. Cancer Sci. 2018;109:84–93.CrossRefPubMed
40.
Gao J, Zhu H, Wan H, Zou X, Ma X, Gao G. Harmine suppresses the proliferation and migration of human ovarian cancer cells through inhibiting ERK/CREB pathway. Oncol Rep. 2017;38:2927–34.CrossRefPubMed
41.
Wang Y, Kuang H, Xue J, Liao L, Yin F, Zhou X. LncRNA AB073614 regulates proliferation and metastasis of colorectal cancer cells via the PI3K/AKT signaling pathway. Biomed Pharmacother. 2017;93:1230–7.CrossRefPubMed
Metadata
Title
Cross-linked hyaluronan gel inhibits the growth and metastasis of ovarian carcinoma
Publication date
01-12-2018
Published in
Journal of Ovarian Research / Issue 1/2018
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/s13048-018-0394-z

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