Anti-cancer Potential of Hydatid Cyst-Derived Antigens: In Vivo Insights

Main Article Content

Zeinab Hosseini
Mohaddeseh Jamali
Nikoo Sadat Hasheminezhad
Razieh Razmi
Rezvan Abbasi
Negar Jahani
Mahsa Mohammadian

Abstract

The global healthcare challenge of cancer remains challenging, requiring innovative approaches to identify potential anticancer agents. The intriguing anti-tumor properties of hydatid cysts produced in their larval stage by Echinococcus granulosus (E. granulosus) have attracted the attention of many scientists in recent years. This review aimed to delve deeper into the in vivo anticancer effects of hydatid cyst-derived antigens and shed light on their mechanisms of action and therapeutic implications for various cancer types. Several bioactive molecules in E. granulosus antigens have shown significant anti-cancer activity in vivo. Several studies have shown that administering these antigens reduced tumor size while increasing overall survival in breast cancer models. The immune response against tumor cells in lung cancer murine models has also been enhanced by E. granulosus antigens, such as antigen B, leading to the regression of tumors and enhanced immunity. Colon cancer cells are sensitized to these antigens as indicated by in vivo studies, rendering standard chemotherapy more effective at inhibiting tumor growth. E. granulosus antigens also reduce tumor metastasis when applied to in vivo melanoma models. E. granulosus antigens have demonstrated in vivo efficacy as a potential anticancer agent, underscoring their potential as valuable therapeutic agents. There is still much to be discovered about the exact mechanisms of these antigens and their clinical applicability. However, the impressive results observed across a wide range of cancer types underscore the significance of further research into the antigens to overcome cancer in vivo. In conclusion, animal model studies reveal the promising potential of E. granulosus antigens, particularly hydatid cyst fluid, in inhibiting tumor growth in colon, breast, melanoma, and lung cancers through immune-mediated mechanisms and apoptosis induction. These findings open up new avenues for cancer therapy and immunotherapy research, emphasizing the role of parasite antigens in combatting various cancer types.

Article Details

How to Cite
Hosseini, Z., Jamali, M., Sadat Hasheminezhad, N., Razmi, R., Abbasi, R., Jahani, N., & Mohammadian, M. (2023). Anti-cancer Potential of Hydatid Cyst-Derived Antigens: In Vivo Insights. Journal of Lab Animal Research, 2(5), 33–40. https://doi.org/10.58803/jlar.v2i5.26
Section
Review Article

References

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: Cancer J Clinic. 2018; 68(6): 394-424. DOI: https://doi.org/10.3322/caac.21492

Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Piñeros M, Znaor A and Bray F. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019; 144(8): 1941-1953. DOI: https://doi.org/10.1002/ijc.31937

Hricak H, Ward ZJ, Atun R, Abdel-Wahab M, Muellner A and Scott AM. Increasing access to imaging for addressing the global cancer epidemic. Radiol Soci N Am. 2021; 301(3): 543-546. DOI: https://doi.org/10.1148/radiol.2021211351

Sadr S and Borji H. Echinococcus granulosus as a Promising Therapeutic Agent against Triplenegative Breast Cancer. Curr Cancer Ther Rev. 2023; 19(4): 292-297. DOI: https://doi.org/10.2174/1573394719666230427094247

Sadr S, Ghiassi S, Lotfalizadeh N, Simab PA, Hajjafari A and Borji H. Antitumor Mechanisms of Molecules Secreted by Trypanosoma cruzi in Colon and Breast Cancer: A Review. Anticancer Agents Med Chem. 2023; 23(15): 1710-1721. DOI: https://doi.org/10.2174/1871520623666230529141544

Asouli A, Sadr S, Mohebalian H and Borji H. Anti-Tumor Effect of Protoscolex Hydatid Cyst Somatic Antigen on Inhibition Cell Growth of K562. Acta Parasitologica. 2023; 1-8. DOI: https://doi.org/10.1007/s11686-023-00680-3

Sadr S, Yousefsani Z, Simab PA, Alizadeh HJR, Lotfalizadeh A and Borji H. Trichinella spiralis as a Potential Antitumor Agent: An Update. World’s Vet J. 2023; 13: 65-74. DOI: https://doi.org/10.54203/scil.2023.wvj7

Yousofi Darani H, Soozangar N, Khorami S, Taji F, Yousofi M and Shirzad H. Hydatid cyst protoscolices induce cell death in WEHI-164 fibrosarcoma cells and inhibit the proliferation of baby hamster kidney fibroblasts in vitro. J Parasitol Res. 2012; 2012. DOI: https://doi.org/10.1155/2012/304183

Ranasinghe SL and McManus DP. Echinococcus granulosus: cure

for cancer revisited. Front Med. 2018; 5: 60. DOI: https://doi.org/10.3389/fmed.2018.00060

Hosch W, Junghanss T, Stojkovic M, Brunetti E, Heye T, Kauffmann GW and Hull WE. Metabolic viability assessment of cystic echinococcosis using high‐field 1H MRS of cyst contents. NMR Biomed: Int J Devot Develop App Magnet Resonance In vivo. 2008; 21(7): 734-754. DOI: https://doi.org/10.1002/nbm.1252

Shojaeian A, Barati N and Motavallihaghi S. Investigating the Inhibitory Effects of Hydatid Cyst Fluid and its Antigens on Cancer Progression: A Review. 2023; DOI: https://doi.org/10.20944/preprints202307.2141.v1

Chookami MB, Sharafi SM, Sefiddashti RR, Jafari R, Bahadoran M, Pestechian N and Darani HY. Effect of two hydatid cyst antigens on the growth of melanoma cancer in C57/black mice. J Parasit Dis. 2016; 40: 1170-1173. DOI: https://doi.org/10.1007/s12639-015-0643-7

Berriel E, Freire T, Chiale C, Rodríguez E, Morón G, Fernandez-Grana G, Crispo M, Berois N and Osinaga E. Human hydatid cyst fluid-induced therapeutic anti-cancer immune responses via NK1. 1+ cell activation in mice. Cancer Immunol, Immunothe 2021; 70(12): 3617-3627. DOI: https://doi.org/10.1007/s00262-021-02948-x

Kudelka MR, Ju T, Heimburg-Molinaro J and Cummings RD. Simple sugars to complex disease—mucin-type O-glycans in cancer. Adv Cancer Res. 2015; 126: 153-135. DOI: https://doi.org/10.1016/bs.acr.2014.11.002

Oliveira-Ferrer L, Legler K and Milde-Langosch K. Role of protein glycosylation in cancer metastasis. Semin Cancer Bio. 2017; 44: 141-152. DOI: https://doi.org/10.1016/j.semcancer.2017.03.002

Casaravilla C, Freire T, Malgor R, Medeiros A, Osinaga E and Carmona C. Mucin-type O-glycosylation in helminth parasites from major taxonomic groups: evidence for widespread distribution of the Tn antigen (GalNAc-Ser/Thr) and identification of UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferase activity. J Parasitol. 2003; 89(4): 709-714. DOI: https://doi.org/10.1645/GE-2970

Parkinson J, Wasmuth J, Salinas G, Bizarro C and Sanford C. A Transcriptomic Analysis of Echinococcus granulosus Larval

Stages. 2012; DOI: https://doi.org/10.1371/annotation/984cd209-4e98-467c-b462-c11090e43be7

Hajizadeh M, Amni F, Sahlolbei M, Tavakoli-yaraki M, Mamaghani AJ, Sefiddashti RR and Rezaee H. Antigen Similarity In Hydatid Cyst Wall And Human Bone Tumours: A Short Report. 2021; DOI: https://doi.org/10.21203/rs.3.rs-411912/v1

Noya V, Bay S, Festari MF, García EP, Rodriguez E, Chiale C, Ganneau C, Baleux F, Astrada S, Bollati-Fogolín M, Osinaga E and Freire T. Mucin-like peptides from Echinococcus granulosus induce anti-tumor activity. Int J Oncol. 2013; 43(3): 775-784. DOI: https://doi.org/10.3892/ijo.2013.2000

Karadayi S, Arslan S, Sumer Z, Turan M, Sumer H and Karadayi K. Does hydatid disease have protective effects against lung cancer? Molecular biology reports. 2013; 40: 4701-4704. DOI: https://doi.org/10.1007/s11033-013-2565-8

Zhang W and McManus DP. Recent advances in the immunology and diagnosis of echinococcosis. FEMS Immunol Med Microbiol. 2006; 47(1): 24-41. DOI: https://doi.org/10.1111/j.1574-695X.2006.00060.x

Barati N, Tanzadehpanah H, Asl SS, Khazaei S and Motavallihaghi S. 2022;

Wang Y, Xiao D, Shen Y, Han X, Zhao F, Li X, Wu W, Zhou H, Zhang J and Cao J. Proteomic analysis of the excretory/secretory products and antigenic proteins of Echinococcus granulosus adult worms from infected dogs. BMC Vet Res. 2015; 11: 1-7. DOI: https://doi.org/10.1186/s12917-015-0423-8

Rahman WA, Elmajdoub L, Noor S and Wajidi M. Present status on the taxonomy and morphology of Echinococcus granulosus: A review. Austin J Vet Sci Anim Husb. 2015; 2(2). DOI:

Tlamcani Z. Hydatidosis in Morocco: Review of literature and epidemiology. Afro-Egypt J Inf Endem Dis. 2016; 6(3): 152-155. DOI: https://doi.org/10.21608/aeji.2016.9962

Grosso G, Gruttadauria S, Biondi A, Marventano S and Mistretta A. Worldwide epidemiology of liver hydatidosis including the Mediterranean area. World J Gastroenterol. 2012; 18(13): 1425-1437. DOI: https://doi.org/10.3748/wjg.v18.i13.1425

Kumsa B and Mohammedzein A. Prevalence, organ distribution, risk factors, and financial losses of hydatid cysts in sheep and goats slaughtered in restaurants in Jimma, south western Oromia. Comparative Clin Pathol. 2012; 23(2): 333-339. DOI: https://doi.org/10.1007/s00580-012-1619-y

Hughes J and Macdonald DW. A review of the interactions between free-roaming domestic dogs and wildlife. Bio Conser. 2013; 157: 341-351. DOI: https://doi.org/10.1016/j.biocon.2012.07.005

Hayashi N, Kouguchi H, Imasato Y, Irie T, Yagi K, Nonaka N and Nakao R. Early-phase migration dynamics of Echinococcus multilocularis in two mouse strains showing different infection susceptibilities. Int J Parasitol. 2021; 51(11): 893-898. DOI: https://doi.org/10.1016/j.ijpara.2021.04.001

Gessese AT, Mulate B, Nazir S and Asmare A. Major metacestodes in small ruminants slaughtered at Dessie municipal abattoir, Eastern Ethiopia: prevalence, cyst viability, organ distribution and economic implications. Compar Clin Pathol. 2015; 24: 659-668. DOI: https://doi.org/10.1007/s00580-014-1964-0

Sadr S, Charbgoo A, Borji H and Hajjafari A. Interactions between innate immunity system and Echinococcus granulosus: permission for vaccine development. Series Med Sci. 2022; 3(1): 1-18. Avaialbale at: https://seriesscience.com/wp-content/uploads/2023/01/Interactions-between-Innate-Immunity.pdf

Raether W and Hänel H. Epidemiology, clinical manifestations and diagnosis of zoonotic cestode infections: an update. Parasitol Res. 2003; 91(5): 412-438. DOI: https://doi.org/10.1007/s00436-003-0903-9

Eckert J, Gemmell M, Meslin F-X, Pawlowski Z and Organization WH. WHO/OIE manual on echinococcosis in humans and animals: a public health problem of global concern. World Organis Anim Health. 2001; DOI:

Siles-Lucas M, Casulli A, Conraths FJ and Muller N. Laboratory Diagnosis of Echinococcus spp. in Human Patients and Infected Animals. Adv Parasitol. 2017; 96: 159-257. DOI: https://doi.org/10.1016/bs.apar.2016.09.003

Sweatman G and Williams R. Comparative studies on the biology and morphology of Echinococcus granulosus from domestic livestock, moose and reindeer. Parasitol. 1963; 53(3-4): 339-390. DOI: https://doi.org/10.1017/S0031182000073832

Shojaeian A, Barati N and Motavallihaghi S. Investigating the Inhibitory Effects of Hydatid Cyst Fluid and its Antigens on Cancer Progression: A Review. 2023; DOI: https://doi.org/10.20944/preprints202307.2141.v1

Siracusano A, Delunardo F, Teggi A, Ortona E. Host-parasite relationship in cystic echinococcosis: an evolving story. J Immunol Res. 2012; 639362. DOI: https://doi.org/10.1155/2012/639362

Han X, Zhou Y and Liu W. Precision cardio-oncology: understanding the cardiotoxicity of cancer therapy. NPJ Precisi Oncol. 2017; 1(1): 31. DOI: https://doi.org/10.1038/s41698-017-0034-x

Ikemoto S, Sugimura K, Yoshida N, Yasumoto R, Wada S, Yamamoto K and Kishimoto T. Anti-tumor effects of Scutellariae radix and its components baicalein, baicalin, and wogonin on bladder cancer cell lines. Urol. 2000; 55(6): 951-955. DOI: https://doi.org/10.1016/S0090-4295(00)00467-2

Shooraj M, Hajipour E and Mahdavi SA. Immunological Examination of Echinococcus granulosus as a Candidate for Cancer Treatment and Vaccine Development: A Review Study. Tabari Biomed Stu Res J. 2022; 4(3): 40-48. DOI: https://doi.org/10.18502/tbsrj.v4i3.10516

Guan W, Zhang X, Wang X, Lu S, Yin J and Zhang J. Employing parasite against cancer: a lesson from the canine tapeworm Echinococcus granulocus. Front Pharmacol. 2019; 10: 1137. DOI: https://doi.org/10.3389/fphar.2019.01137

Darani HY and Yousefi M. Parasites and cancers: parasite antigens as possible targets for cancer immunotherapy. Future Oncol. 2012; 8(12): 1529-1535. DOI: https://doi.org/10.2217/fon.12.155

Ditgen D, Anandarajah EM, Hansmann J, Winter D, Schramm G, Erttmann KD, Liebau E and Brattig NW. Multifunctional thioredoxin-like protein from the gastrointestinal parasitic nematodes Strongyloides ratti and Trichuris suis affects mucosal homeostasis. J Parasitol Res. 2016; 2016. DOI: https://doi.org/10.1155/2016/8421597

Darani HY. Effect of hydatid cyst antigens on inhibition of melanoma cancer growth in mouse model. Cell Mol Biol. 2018; 64(12): 1-6. DOI: https://doi.org/10.14715/cmb/2018.64.12.1

Van der Weijden J, Paulis LE, Verdoes M, van Hest JC and Figdor CG. The right touch: design of artificial antigen-presenting cells to stimulate the immune system. Chem Sci. 2014; 5(9): 3355-3367. DOI: https://doi.org/10.1039/C4SC01112K

Farinon M, Oliveira P, Clarimundo V, Monteiro K, Zaha A, Ferreira H and Xavier RM. AB0135 Immunomodulatory and Antiinflammatory Properties of Antigen B, A Protein Secreted by Echinococcus Granulosus Larval Stage, in Experimental Arthritis. Annal Rheumatic Dis. 2014; 73(Suppl 2): 848-848. DOI: https://doi.org/10.1136/annrheumdis-2014-eular.3897

Nono JK, Pletinckx K, Lutz MB and Brehm K. Excretory/secretory-products of Echinococcus multilocularis larvae induce apoptosis and tolerogenic properties in dendritic cells in vitro. PLoS Neglect Tropi Dis. 2012; 6(2): e1516. DOI: https://doi.org/10.1371/journal.pntd.0001516

Wysocka J, Reilly PT and Herr W. Loss of HCF-1–chromatin association precedes temperature-induced growth arrest of tsBN67 cells. Mol Cell Bio. 2001; 21(11): 3820-3829. DOI: https://doi.org/10.1128/MCB.21.11.3820-3829.2001

Huang S. Regulation of metastases by signal transducer and activator of transcription 3 signaling pathway: clinical implications. Clin Cancer Res. 2007; 13(5): 1362-1366. DOI: https://doi.org/10.1158/1078-0432.CCR-06-2313

Gupta SC, Kim JH, Prasad S and Aggarwal BB. Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals. Cancer Metastas Rev. 2010; 29: 405-434. DOI: https://doi.org/10.1007/s10555-010-9235-2

Mouhid L, Gómez de Cedrón M, García-Carrascosa E, Reglero G, Fornari T and Ramírez de Molina A. Yarrow supercritical extract exerts antitumoral properties by targeting lipid metabolism in pancreatic cancer. PloS one. 2019; 14(3): e0214294. DOI: https://doi.org/10.1371/journal.pone.0214294

Shakibapour M, Kefayat A, Reza Mofid M, Shojaie B, Mohamadi F, Maryam Sharafi S, Mahmoudzadeh M and Darani HY. Anti-cancer immunoprotective effects of immunization with hydatid cyst wall antigens in a non-immunogenic and metastatic triple-negative murine mammary carcinoma model. Int Immunopharmacol. 2021 ;99: 107955. DOI: https://doi.org/10.1016/j.intimp.2021.107955

Gundogdu SB, Saylam B and Tez M. Cyst hydatid and cancer: The myth continues. Clin Chem Lab Med (CCLM). 2017; 55(7): e150-e1. DOI: https://doi.org/10.1515/cclm-2016-0626

Diaz A, Casaravilla C, Barrios AA and Ferreira AM. Parasite molecules and host responses in cystic echinococcosis. Parasite Immunol. 2016; 38(3): 193-205. DOI: https://doi.org/10.1111/pim.12282

Asghari A, Nourmohammadi H, Majidiani H, Shariatzadeh SA, Anvari D, Shamsinia S, Ghasemi E, Shams M and Basati G. Promising effects of parasite-derived compounds on tumor regression: a systematic review of in vitro and in vivo studies. Enviro Sci Pollut Res. 2022; 29(22): 32383-32396. DOI: https://doi.org/10.1007/s11356-021-17090-5

Oikonomopoulou K, Yu H, Wang Z, Vasiliou SK, Brinc D, Christofi G, Theodorou M, Pavlou P, Hadjisavvas A, Demetriou CA, Kyriacou K and Diamandis EP. Association between Echinococcus granulosus infection and cancer risk–a pilot study in Cyprus. Clin Chem Lab Med (CCLM). 2016; 54(12): 1955-1961. DOI: https://doi.org/10.1515/cclm-2016-0125

DeNardo DG and Coussens LM. Inflammation and breast cancer. Balancing immune response: crosstalk between adaptive and innate immune cells during breast cancer progression. Breast Cancer Res. 2007; 9: 1-10. DOI: https://doi.org/10.1186/bcr1746

Rostami-Rad S, Jafari R and Darani HY. Th1/Th2-type cytokine profile in C57 black mice inoculated with live Echinococcus granulosus protoscolices. J Inf Pub Health. 2018; 11(6): 834-839. DOI: https://doi.org/10.1016/j.jiph.2018.06.007

Koski GK, Koldovsky U, Xu S, Mick R and Sharma A, Fitzpatrick E, Weinstein S, Nisenbaum H, Levine BL, Fox K, Zhang P, Czerniecki BJ. A novel dendritic cell-based immunization approach for the induction of durable Th1-polarized anti-HER-2/neu responses in women with early breast cancer. J Immunothe (Hagerstown, Md: 1997). 2012; 35(1): 54. DOI: https://doi.org/10.1097/CJI.0b013e318235f512

Berois N, Pittini A and Osinaga E. Targeting tumor glycans for cancer therapy: successes, limitations, and perspectives. Cancer. 2022; 14(3): 645. DOI: https://doi.org/10.3390/cancers14030645

Nodeh FJ, Sharafi SM, Tuloee S, Hejazi SH, Dorosti Z and Darani HY. Effect of passive transfer of anti-hydatid cyst antigen antisera on melanoma tumor growth in animal model. World J Oncol Res. 2015; 2: 1-4. DOI:

Yousefi M, Akbari M, Hadipour M, Dehkordi AB, Farahbakhsh Z and Darani HY. Parasites as potential targets for cancer immunotherapy. J Cancer Res Clin Oncol. 2023; 1-12. DOI: https://doi.org/10.1007/s00432-023-04694-2

Dogan S, Cakir M, Kartal A, Oztas H and Oltulu P. Can Echinococcus Granulosus Infestation Prevent Pancreatic Cancer? An invivo Experimental Study. Asian Pac J Cancer Prev. 2023; 24(4): 1307-1312. DOI: https://doi.org/10.31557/APJCP.2023.24.4.1307

Badri-Chookami M, Sharafi SM, Rafeie R, Bahadoran M, Pestechian N and Yousofi-Darani H. Effect of Alive Protoscoleces of Hydatid Cyst on the Growth of Melanoma Cells in Mouse Model. J Isfahan Med Sch.

; 32(281): 486-492. Available at: https://jims.mui.ac.ir/ article_14312_8743986d61a8e1edda4d92b198eaed2e.pdf?lang=en

Darani HY, Sharafi SM, Mokarian F, Yousefi M, Sharafi SA and Jafari R. Therapeutic effect of hydatid cyst liquid on melanoma tumor growth in mouse model. British J Med Res. 2016; 18(2): 1-7. DOI: https://doi.org/10.9734/BJMMR/2016/27220

Daneshpour S, reza Mofid M, Andalib A, Eskandariyan A and Darani HY. Effect of hydatid cyst antigens on inhibition of melanoma cancer growth in mouse model. Cell Mol Bio. 2018; 64(12): 1-5. DOI: https://doi.org/10.14715/cmb/2018.64.12.1

Berriel E, Russo S, Monin L, Festari MF, Berois N, Fernandez G, Freire T and Osinaga E. Anti-tumor activity of human hydatid cyst fluid in a murine model of colon cancer. Sci World J. 2013; 2013: 230176. DOI: https://doi.org/10.1155/2013/230176

Rostamirad S, Daneshpour S, Mofid MR, Andalib A, Eskandariyan A, Mousavi S and Drani HY. Inhibition of mouse colon cancer growth following immunotherapy with a fraction of hydatid cyst fluid. Exp Parasitol. 2023; 249: 108501. DOI: https://doi.org/10.1016/j.exppara.2023.108501

Berriel E, Freire T, Chiale C, Rodriguez E, Moron G, Fernandez-Grana G, Crispo M, Berois N and Osinaga E. Human hydatid cyst fluid-induced therapeutic anti-cancer immune responses via NK1.1(+) cell activation in mice. Cancer Immunol Immunother. 2021; 70(12): 3617-3627. DOI: https://doi.org/10.1007/s00262-021-02948-x

Cao S, Gong W, Zhang X, Xu M, Wang Y, Xu Y, Cao J, Shen Y and Chen J. Arginase promotes immune evasion of Echinococcus granulosus in mice. Parasit Vector. 2020; 13(1): 49. DOI: https://doi.org/10.1186/s13071-020-3919-4

Vafae Eslahi A, Ghaffarifar F, Muhammad Hassan Z and Dalimi A. Anticancer Activity of Hydatid Cyst Fluid along with Antigen B on Tumors Induced by 4T1 Breast Cancer Cell in a BALB/c Mice Model. Iran J Parasitol. 2022; 17(2): 240-249. DOI: https://doi.org/10.18502/ijpa.v17i2.9542

Daneshpour S, Kefayat AH, Mofid MR, Rostami Rad S and Yousofi Darani H. Effect of Hydatid Cyst Fluid Antigens on Induction of Apoptosis on Breast Cancer Cells. Adv Biomed Res. 2019; 8: 27. DOI: https://doi.org/10.4103/abr.abr_220_18

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