AccScience Publishing / GPD / Online First / DOI: 10.36922/gpd.1848
Submit to GPD
Cite this article
65
Download
1464
Views
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
ORIGINAL RESEARCH ARTICLE

Continuous topical application of microencapsulated recombinant human epidermal growth factor does not promote the progression of established melanoma in animals

Chien-Shan Wu1,2† ,  Jian-Ching Wu3,4† ,  Ching-Min Tseng5,6 ,  Le-Shin Chang7 ,  Chi-Fang Wu8 ,  Yi-Tzu Li8 ,  Yi-Wen Lin8 ,  Ming-Hong Tai3,4,8*
Show Less
1 Department of Dermatology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, Republic of China
2 Department of Dermatology, Pingtung Veterans General Hospital, Pingtung, Taiwan, Republic of China
3 Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University, Kaohsiung, Taiwan, Republic of China
4 Doctoral Degree Program in Marine Biotechnology, Academia Sinica, Taipei, Taiwan, Republic of China
5 Division of Chest Medicine, Department of Internal Medicine, Cheng Hsin General Hospital, Taipei, Taiwan, Republic of China
6 School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taiwan, Republic of China
7 College of Life Sciences, National Chung Hsing University, Taichung, Taiwan, Republic of China
8 Institute of Biomedical Science, National Sun Yat-sen University, Kaohsiung, Taiwan, Republic of China
GPD 2023, 2(4), 1848 https://doi.org/10.36922/gpd.1848
Submitted: 16 September 2023 | Accepted: 20 December 2023 | Published: 29 December 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Download PDF
Cite
XML
Abstract

Microencapsulated epidermal growth factor (EGF) device has been applied topically for the management of several types of wounds to accelerate wound healing and prevent scar formation. However, it remains unclear whether such EGF device induced neoplastic transformation in the skin. In this study, we exploited a well-established murine B16-F10 melanoma model, coupled with MTT viability and colony formation assays, to investigate the influence of microencapsulated recombinant EGF (Me-EGF; brand name NewEpi®) and its ingredients on the tumorigenicity of skin cancer cells in vitro and in vivo. The results indicated that Me-EGF did not stimulate the viability nor the anchorage-dependent growth of B16-F10 melanoma cells. Western blot analysis showed that Me-EGF treatment increased the total and phosphorylated EGFR expression without affecting the HER2 expression in B16-F10 melanoma cells. In mice bearing established B16-F10 melanoma, continuous application of Me-EGF for 14 days did not enhance the melanoma tumor burden compared with control groups. Immunohistochemical analysis also revealed the similar expression of proliferative index Ki-67 between Me-EGF-treated melanoma and other groups. Altogether, these results suggest that the application of Me-EGF device did not promote the oncogenic potential of B16-F10 melanoma in vitro and in vivo.

Keywords
Melanoma
Epidermal growth factor
Microencapsulation
Me-EGF
Funding
Kaohsiung Veterans General Hospital, Taiwan, Republic of China
Conflict of interest
The authors have declared no conflicts of interest.
References
  1. Yao Q, Yu Z, Liu P, et al., 2019, High efficient expression and purification of human epidermal growth factor in Arachis Hypogaea L. Int J Mol Sci, 20(8): 2045. https://doi.org/10.3390/ijms20082045

 

  1. Gurtner GC, Werner S, Barrandon Y, et al., 2008, Wound repair and regeneration. Nature, 453(7193): 314–321. https://doi.org/10.1038/nature07039

 

  1. Werner S, Grose R, 2003, Regulation of wound healing by growth factors and cytokines. Physiol Rev, 83(3): 835–870. https://doi.org/10.1152/physrev.2003.83.3.835

 

  1. Tiaka EK, Papanas N, Manolakis AC, et al., 2012, Epidermal growth factor in the treatment of diabetic foot ulcers: An update. Perspect Vasc Surg Endovasc Ther, 24(1): 37–44. https://doi.org/10.1177/1531003512442093

 

  1. Hardwicke J, Schmaljohann D, Boyce D, et al., 2008, Epidermal growth factor therapy and wound healing--past, present and future perspectives. Surgeon, 6(3): 172–177. https://doi.org/10.1016/s1479-666x(08)80114-x

 

  1. Mao S, Sun W, Kissel T, 2010, Chitosan-based formulations for delivery of DNA and siRNA. Adv Drug Deliv Rev, 62(1): 12–27. https://doi.org/10.1016/j.addr.2009.08.004

 

  1. Kean T, Thanou M, 2010, Biodegradation, biodistribution and toxicity of chitosan. Adv Drug Deliv Rev, 62(1): 3–11. https://doi.org/10.1016/j.addr.2009.09.004

 

  1. Kao CC, Huang SY, Chiang CH, et al., 2021, Microencapsulated rhEGF to facilitate epithelial healing and prevent scar formation of cesarean wound: A randomized controlled trial. Taiwan J Obstet Gynecol, 60(3): 468–473. https://doi.org/10.1016/j.tjog.2021.03.014

 

  1. Tsai HC, Sheng C, Chang LS, et al., 2021, Chitosan-microencapsulated rhEGF in promoting wound healing. J Wound Care, 30(Sup9a): IXi–IXxi. https://doi.org/10.12968/jowc.2021.30.Sup9a.IX

 

  1. Lin SC, Zhang X, Chen SY, et al., 2021, Microencapsulated recombinant human epidermal growth factor ameliorates osteoarthritis in a murine model. Evid Based Complement Alternat Med, 2021: 9163279. https://doi.org/10.1155/2021/9163279

 

  1. Treskova I, Topolcan O, Windrichova J, et al., 2018, OPG, OPN, EGF and VEGF levels at individual breslow score stages in malignant melanoma. Anticancer Res, 38(8): 4907–4911. https://doi.org/10.21873/anticanres.12806

 

  1. Bracher A, Cardona AS, Tauber S, et al., 2013, Epidermal growth factor facilitates melanoma lymph node metastasis by influencing tumor lymphangiogenesis. J Invest Dermatol, 133(1): 230–238. https://doi.org/10.1038/jid.2012.272

 

  1. Shetty G, Beasley GM, Sparks S, et al., 2013, Plasma cytokine analysis in patients with advanced extremity melanoma undergoing isolated limb infusion. Ann Surg Oncol, 20(4): 1128–1135. https://doi.org/10.1245/s10434-012-2785-5

 

  1. Lim YJ, Jeon SR, Koh JM, et al., 2015, Tumor growth suppression and enhanced radioresponse by an exogenous epidermal growth factor in mouse xenograft models with A431 cells. Cancer Res Treat, 47(4): 921–930. https://doi.org/10.4143/crt.2014.153

 

  1. Choi J, Moon SY, Hong JP, et al., 2010, Epidermal growth factor induces cell death in the absence of overexpressed epidermal growth factor receptor and ErbB2 in various human cancer cell lines. Cancer Invest, 28(5): 505–514. https://doi.org/10.3109/07357900902783179

 

  1. Lee DW, Lim C, Israelachvili JN, et al., 2013, Strong adhesion and cohesion of chitosan in aqueous solutions. Langmuir, 29(46): 14222–14229. https://doi.org/10.1021/la403124u

 

  1. Andrade F, Goycoolea F, Chiappetta DA, et al., 2011, Chitosan-grafted copolymers and chitosan-ligand conjugates as matrices for pulmonary drug delivery. Int J Carbohydr Chem, 2011: 865704. https://doi.org/10.1155/2011/865704

 

  1. Liu GS, Liu LF, Lin CJ, et al., 2006, Gene transfer of pro-opiomelanocortin prohormone suppressed the growth and metastasis of melanoma: Involvement of alpha-melanocyte-stimulating hormone-mediated inhibition of the nuclear factor kappaB/cyclooxygenase-2 pathway. Mol Pharmacol, 69(2): 440–451. https://doi.org/10.1124/mol.105.015404

 

  1. Wang W, Xue C, Mao X, 2020, Chitosan: Structural modification, biological activity and application. Int J Biol Macromol, 164: 4532–4546. https://doi.org/10.1016/j.ijbiomac.2020.09.042

 

  1. Kim S, Gaber MW, Zawaski JA, et al., 2009, The inhibition of glioma growth in vitro and in vivo by a chitosan/ellagic acid composite biomaterial. Biomaterials, 30(27): 4743–4751. https://doi.org/10.1016/j.biomaterials.2009.05.010

 

  1. Nam KS, Shon YH, 2009, Suppression of metastasis of human breast cancer cells by chitosan oligosaccharides. J Microbiol Biotechnol, 19(6): 629–633. https://doi.org/10.4014/jmb.0811.603

 

  1. Liu GS, Tsai HE, Weng WT, et al., 2011, Systemic pro-opiomelanocortin expression induces melanogenic differentiation and inhibits tumor angiogenesis in established mouse melanoma. Hum Gene Ther, 22(3): 325–335. https://doi.org/10.1089/hum.2010.090

 

  1. Wu JC, Tsai HE, Hsiao YH, et al., 2020, Topical MTII therapy suppresses melanoma through PTEN upregulation and cyclooxygenase II inhibition. Int J Mol Sci, 21(2): 681. https://doi.org/10.3390/ijms21020681

 

  1. Weng CH, Wu CS, Wu JC, et al., 2020, Cisplatin-induced giant cells formation is involved in chemoresistance of melanoma cells. Int J Mol Sci, 21(21): 7892. https://doi.org/10.3390/ijms21217892

 

  1. Majumder A, Sandhu M, Banerji D, et al., 2021, The role of HER2 and HER3 in HER2-amplified cancers beyond breast cancers. Sci Rep, 11(1): 9091. https://doi.org/10.1038/s41598-021-88683-w

 

  1. Watanabe S, Yonesaka K, Tanizaki J, et al., 2019, Targeting of the HER2/HER3 signaling axis overcomes ligand-mediated resistance to trastuzumab in HER2-positive breast cancer. Cancer Med, 8(3): 1258–1268. https://doi.org/10.1002/cam4.1995

 

  1. Krahn G, Leiter U, Kaskel P, et al., 2001, Coexpression patterns of EGFR, HER2, HER3 and HER4 in non-melanoma skin cancer. Eur J Cancer, 37(2): 251–259. https://doi.org/10.1016/s0959-8049(00)00364-6

 

  1. Liu S, Geng R, Lin E, et al., 2021, ERBB1/2/3 expression, prognosis, and immune infiltration in cutaneous melanoma. Front Genet, 12: 602160. https://doi.org/10.3389/fgene.2021.602160

 

  1. Ma J, Han H, Liu D, et al., 2013, HER2 as a promising target for cytotoxicity T cells in human melanoma therapy. PLoS One, 8(8): e73261. https://doi.org/10.1371/journal.pone.0073261

 

  1. Pudelko K, Wieland A, Hennecke M, et al., 2022, Increased microtubule growth triggered by microvesicle-mediated paracrine signaling is required for melanoma cancer cell invasion. Cancer Res Commun, 2(5): 366–379. https://doi.org/10.1158/2767-9764.CRC-22-0010

 

  1. Wu HG, Song SY, Kim YS, et al., 2009, Therapeutic effect of recombinant human epidermal growth factor (RhEGF) on mucositis in patients undergoing radiotherapy, with or without chemotherapy, for head and neck cancer: A double-blind placebo-controlled prospective phase 2 multi-institutional clinical trial. Cancer, 115(16): 3699–3708. https://doi.org/10.1002/cncr.24414

 

  1. Wang GY, Xia ZF, Zhu SH, et al., 2003, Clinical observation of the long-term effects of rhEGF on deep partial-thickness burn wounds. Zhonghua Shao Shang Za Zhi, 19(3): 167–168.
Share
Back to top
Gene & Protein in Disease, Electronic ISSN: 2811-003X Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept