Immunotherapeutic Potential of Mollusk Hemocyanins in Murine Model of Melanoma

Overview

Journal Mar Drugs

Publisher MDPI

Specialties Biology
Pharmacology

Date 2024 May 24

PMID 38786612

Authors

Emiliya Stoyanova

Nikolina Mihaylova

Nikola Ralchev

Silviya Bradyanova

Iliyan Manoylov

Yuliana Raynova

Krassimira Idakieva

Andrey Tchorbanov

Affiliations

Soon will be listed here.

Abstract

Materials And Methods: We established a murine model of melanoma by challenging C57BL/6 mice with a B16F10 cell line for solid tumor formation in experimental animals. The anticancer properties of hemocyanins isolated from the marine snail (RtH) and the terrestrial snail (HaH) were evaluated in this melanoma model using various schemes of therapy. Flow cytometry, ELISA, proliferation, and cytotoxicity assays, as well as histology investigations, were also performed.

Results: Beneficial effects on tumor growth, tumor incidence, and survival of tumor-bearing C57BL/6 mice after administration of the RtH or HaH were observed. The generation of high titers of melanoma-specific IgM antibodies, pro-inflammatory cytokines, and tumor-specific CTLs, and high levels of tumor-infiltrated M1 macrophages enhanced the immune reaction and tumor suppression.

Discussion: Both RtH and HaH exhibited promising properties for applications as antitumor therapeutic agents and future experiments with humans.

Citing Articles

hemocyanin as a novel natural immunostimulant in mammals.

Chiumiento I, Tricerri M, Cortez M, Ituarte S, Tau J, Marino K Front Immunol. 2025; 15():1490260.

PMID: 39845952 PMC: 11750813. DOI: 10.3389/fimmu.2024.1490260.

Modified Hemocyanins from and Exhibit Strong Antitumor Activity in the B16F10 Mouse Melanoma Model.

Stoyanova E, Mihaylova N, Ralchev N, Bradyanova S, Manoylov I, Raynova Y Mar Drugs. 2024; 22(10).

PMID: 39452870 PMC: 11509262. DOI: 10.3390/md22100462.

References

Zhong T, Arancibia S, Born R, Tampe R, Villar J, Del Campo M . Hemocyanins Stimulate Innate Immunity by Inducing Different Temporal Patterns of Proinflammatory Cytokine Expression in Macrophages. J Immunol. 2016; 196(11):4650-62. PMC: 4873724. DOI: 10.4049/jimmunol.1501156. View

Diaz-Zaragoza M, Hernandez-Avila R, Viedma-Rodriguez R, Arenas-Aranda D, Ostoa-Saloma P . Natural and adaptive IgM antibodies in the recognition of tumor-associated antigens of breast cancer (Review). Oncol Rep. 2015; 34(3):1106-14. PMC: 4530904. DOI: 10.3892/or.2015.4095. View

Cordell G . Biodiversity and drug discovery--a symbiotic relationship. Phytochemistry. 2000; 55(6):463-80. DOI: 10.1016/s0031-9422(00)00230-2. View

Tchorbanov A, Idakieva K, Mihaylova N, Doumanova L . Modulation of the immune response using Rapana thomasiana hemocyanin. Int Immunopharmacol. 2008; 8(7):1033-8. DOI: 10.1016/j.intimp.2008.03.008. View

Zhang M, Di Martino J, Bowman R, Campbell N, Baksh S, Simon-Vermot T . Adipocyte-Derived Lipids Mediate Melanoma Progression via FATP Proteins. Cancer Discov. 2018; 8(8):1006-1025. PMC: 6192670. DOI: 10.1158/2159-8290.CD-17-1371. View

Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin D, Pineros M . Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2018; 144(8):1941-1953. DOI: 10.1002/ijc.31937. View

Bellenghi M, Puglisi R, Pontecorvi G, De Feo A, Care A, Mattia G . Sex and Gender Disparities in Melanoma. Cancers (Basel). 2020; 12(7). PMC: 7408637. DOI: 10.3390/cancers12071819. View

Gesheva V, Idakieva K, Kerekov N, Nikolova K, Mihaylova N, Doumanova L . Marine gastropod hemocyanins as adjuvants of non-conjugated bacterial and viral proteins. Fish Shellfish Immunol. 2010; 30(1):135-42. DOI: 10.1016/j.fsi.2010.09.018. View

Presicce P, Taddeo A, Conti A, Villa M, Della Bella S . Keyhole limpet hemocyanin induces the activation and maturation of human dendritic cells through the involvement of mannose receptor. Mol Immunol. 2007; 45(4):1136-45. DOI: 10.1016/j.molimm.2007.07.020. View

10.

Strizova Z, Benesova I, Bartolini R, Novysedlak R, Cecrdlova E, Koumbas Foley L . M1/M2 macrophages and their overlaps - myth or reality?. Clin Sci (Lond). 2023; 137(15):1067-1093. PMC: 10407193. DOI: 10.1042/CS20220531. View

11.

Aarntzen E, de Vries I, Goertz J, Beldhuis-Valkis M, Brouwers H, van de Rakt M . Humoral anti-KLH responses in cancer patients treated with dendritic cell-based immunotherapy are dictated by different vaccination parameters. Cancer Immunol Immunother. 2012; 61(11):2003-11. PMC: 3493659. DOI: 10.1007/s00262-012-1263-z. View

12.

Raynova Y, Doumanova L, Idakieva K . Phenoloxidase activity of Helix aspersa maxima (garden snail, gastropod) hemocyanin. Protein J. 2013; 32(8):609-18. DOI: 10.1007/s10930-013-9523-0. View

13.

Todinova S, Raynova Y, Idakieva K . Calorimetric Study of Maxima Hemocyanin Isoforms. J Anal Methods Chem. 2018; 2018:8450792. PMC: 5857327. DOI: 10.1155/2018/8450792. View

14.

Palacios M, Tampe R, Del Campo M, Zhong T, Lopez M, Salazar-Onfray F . Antitumor activity and carrier properties of novel hemocyanins coupled to a mimotope of GD2 ganglioside. Eur J Med Chem. 2018; 150:74-86. DOI: 10.1016/j.ejmech.2018.02.082. View

15.

Kato S, Matsui T, Gatsogiannis C, Tanaka Y . Molluscan hemocyanin: structure, evolution, and physiology. Biophys Rev. 2017; 10(2):191-202. PMC: 5899709. DOI: 10.1007/s12551-017-0349-4. View

16.

Vanneman M, Dranoff G . Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer. 2012; 12(4):237-51. PMC: 3967236. DOI: 10.1038/nrc3237. View

17.

Gesheva V, Chausheva S, Stefanova N, Mihaylova N, Doumanova L, Idakieva K . Helix pomatia hemocyanin - a novel bio-adjuvant for viral and bacterial antigens. Int Immunopharmacol. 2015; 26(1):162-8. DOI: 10.1016/j.intimp.2015.03.011. View

18.

Arancibia S, Del Campo M, Nova E, Salazar F, Becker M . Enhanced structural stability of Concholepas hemocyanin increases its immunogenicity and maintains its non-specific immunostimulatory effects. Eur J Immunol. 2011; 42(3):688-99. DOI: 10.1002/eji.201142011. View

19.

Arancibia S, Espinoza C, Salazar F, Del Campo M, Tampe R, Zhong T . A novel immunomodulatory hemocyanin from the limpet Fissurella latimarginata promotes potent anti-tumor activity in melanoma. PLoS One. 2014; 9(1):e87240. PMC: 3900722. DOI: 10.1371/journal.pone.0087240. View

20.

Mathur S, Hoskins C . Drug development: Lessons from nature. Biomed Rep. 2017; 6(6):612-614. PMC: 5449954. DOI: 10.3892/br.2017.909. View