The effect of leg ischemia/reperfusion injury on the liver in an experimental breast cancer model

Yıl 2021, , 1079 - 1085, 01.11.2021

Murathan Erkent , Güneş Dinç Akbulut , Utku Horzum , Çisel Aydın Meriçöz Güneş Esendağlı

https://doi.org/10.28982/josam.1003837

Öz

Background/Aim: Ischemia/reperfusion (I/R) injury occurs during breast cancer surgery, especially those involving a modified radical mastectomy, lumpectomy, and axillary lymph node dissection. Tissue damage and stress due to I/R alter immune system functions, especially those of the myeloid cells. The immunologic impact of this I/R injury on myeloid-derived cancerous cells remains unknown. We sought to investigate the effect of I/R injury in the extremity close the breast tumor location on myeloid cell population in the liver and liver metastasis.
Methods: 4T1 breast tumors were created in the left inguinal breast region of the experimental animals. When the tumor reached 0.5 cm in diameter, ischemia was produced on the left down-extremity for 90 min and reperfusion was induced for short (3 days), middle (7 days), and long terms (14 days). At the end of the reperfusion period, proximal limbs and livers were harvested. The limb and liver samples were histopathologically examined with H&E staining. Immune cell percentages were determined in the liver by flow cytometry.
Results: There was an increase in muscle fiber degeneration and disorganization in the I/R induced proximal legs on days 3 and 7 of I/R in both tumor free and tumor bearing animals with a further impact in tumor bearing mice. Even though I/R injury did not affect tumor metastasis to the liver, it had an impact on liver myeloid cell percentages in both tumor free and tumor bearing animals. Additionally, tumor bearing mice demonstrated higher myeloid cell percentages in both the pre-I/R and post-I/R experimental groups. There was a remarkable change in the levels of granulocytic, and monocytic myeloid cells and macrophages due to the I/R injury.
Conclusion: With the formation of short-term I/R injury in a distant site, tumor development and/or seeding to metastasis sites after surgery could be prevented. This study contributes to the understanding of the inflammatory process after I/R injury occurring during interventions.

Anahtar Kelimeler

Breast cancer, Ischemia, I/R injury, Myeloid cells, MDSCs, Liver

Destekleyen Kurum

There is no funding

Proje Numarası

2015/46-07

Teşekkür

We thank Prof. Dr. Derya KARAKOC in Department of General Surgery, Medical School of Hacettepe University for the technical support and her supervision.

Kaynakça

• 1. https://www.who.int/activities/preventing-cancer.
• 2. https://www.who.int/cancer/prevention/diagnosis-screening/breast-cancer/en/.
• 3. Bulkley GB. Free radical-mediated reperfusion injury: a selective review. Br J Cancer Suppl. 1987;8:66-73. Epub 1987/06/01. PubMed PMID: 3307876.
• 4. Barry MC, Kelly C, Burke P, Sheehan S, Redmond HP, Bouchier-Hayes D. Immunological and physiological responses to aortic surgery: effect of reperfusion on neutrophil and monocyte activation and pulmonary function. Br J Surg. 1997;84(4):513-9. Epub 1997/04/01. PubMed PMID: 9112905.
• 5. Esme H, Fidan H, Koken T, Solak O. Effect of lung ischemia--reperfusion on oxidative stress parameters of remote tissues. Eur J Cardiothorac Surg. 2006;29(3):294-8. Epub 2006/01/28. doi: 10.1016/j.ejcts.2005.12.008. PubMed PMID: 16439150.
• 6. Vaghasiya JD, Sheth NR, Bhalodia YS, Jivani NP. Exaggerated liver injury induced by renal ischemia reperfusion in diabetes: effect of exenatide. Saudi J Gastroenterol. 2010;16(3):174-80. Epub 2010/07/10. doi: 10.4103/1319-3767.65187. PubMed PMID: 20616412.
• 7. Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol. 2012;298:229-317. Epub 2012/08/11. doi: 10.1016/B978-0-12-394309-5.00006-7. PubMed PMID: 22878108.
• 8. Altamirano F, Wang ZV, Hill JA. Cardioprotection in ischaemia-reperfusion injury: novel mechanisms and clinical translation. J Physiol. 2015;593(17):3773-88. Epub 2015/07/15. doi: 10.1113/JP270953. PubMed PMID: 26173176.
• 9. Ong SB, Gustafsson AB. New roles for mitochondria in cell death in the reperfused myocardium. Cardiovasc Res. 2012;94(2):190-6. Epub 2011/11/24. doi: 10.1093/cvr/cvr312. PubMed PMID: 22108916.
• 10. Karatzas T, Neri AA, Baibaki ME, Dontas IA. Rodent models of hepatic ischemia-reperfusion injury: time and percentage-related pathophysiological mechanisms. J Surg Res. 2014;191(2):399-412. Epub 2014/07/19. doi: 10.1016/j.jss.2014.06.024. PubMed PMID: 25033703.
• 11. Ferrari RS, Andrade CF. Oxidative Stress and Lung Ischemia-Reperfusion Injury. Oxid Med Cell Longev. 2015;2015:590987. Epub 2015/07/15. doi: 10.1155/2015/590987. PubMed PMID: 26161240.
• 12. Fan C, Zwacka RM, Engelhardt JF. Therapeutic approaches for ischemia/reperfusion injury in the liver. J Mol Med (Berl). 1999;77(8):577-92. Epub 1999/10/30. doi: 10.1007/s001099900029. PubMed PMID: 10543390.
• 13. Elias-Miro M, Jimenez-Castro MB, Rodes J, Peralta C. Current knowledge on oxidative stress in hepatic ischemia/reperfusion. Free Radic Res. 2013;47(8):555-68. Epub 2013/06/07. doi: 10.3109/10715762.2013.811721. PubMed PMID: 23738581.
• 14. Rodrigues SF, Granger DN. Role of blood cells in ischaemia-reperfusion induced endothelial barrier failure. Cardiovasc Res. 2010;87(2):291-9. Epub 2010/03/20. doi: 10.1093/cvr/cvq090. PubMed PMID: 20299333.
• 15. Ioannou A, Dalle Lucca J, Tsokos GC. Immunopathogenesis of ischemia/reperfusion-associated tissue damage. Clin Immunol. 2011;141(1):3-14. Epub 2011/08/16. doi: 10.1016/j.clim.2011.07.001. PubMed PMID: 21839685.
• 16. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001;357(9255):539-45. Epub 2001/03/07. doi: 10.1016/S0140-6736(00)04046-0. PubMed PMID: 11229684.
• 17. Rakoff-Nahoum S. Why cancer and inflammation? Yale J Biol Med. 2006;79(3-4):123-30. Epub 2007/10/18. PubMed PMID: 17940622.
• 18. Akbulut GD, Özkazanç, D. , Esendağlı, G. Th1 cells in cancer-associated inflammation. Turkish Journal of Biology. 2017;41(1):20-30.
• 19. Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009;9(3):162-74. doi: 10.1038/nri2506. PubMed PMID: 19197294.
• 20. Bronte V, Brandau S, Chen SH, Colombo MP, Frey AB, Greten TF, et al. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat Commun. 2016;7:12150. Epub 2016/07/07. doi: 10.1038/ncomms12150. PubMed PMID: 27381735.
• 21. Markowitz J, Wesolowski R, Papenfuss T, Brooks TR, Carson WE, 3rd. Myeloid-derived suppressor cells in breast cancer. Breast Cancer Res Treat. 2013;140(1):13-21. Epub 2013/07/06. doi: 10.1007/s10549-013-2618-7. PubMed PMID: 23828498.
• 22. Ilkovitch D, Lopez DM. The liver is a site for tumor-induced myeloid-derived suppressor cell accumulation and immunosuppression. Cancer Res. 2009;69(13):5514-21. Epub 2009/06/25. doi: 10.1158/0008-5472.CAN-08-4625. PubMed PMID: 19549903.
• 23. Audollent R, Eveno C, Contreres JO, Hainaud P, Rampanou A, Dupuy E, et al. Bone marrow-derived endothelial and hematopoietic precursors cells enhance the metastasis of colon cancer in an orthotopic murine model. Int J Cancer. 2011;129(9):2304-5. Epub 2012/06/28. doi: 10.1002/ijc.25882. PubMed PMID: 22736413.
• 24. Orci LA, Lacotte S, Oldani G, Morel P, Mentha G, Toso C. The role of hepatic ischemia-reperfusion injury and liver parenchymal quality on cancer recurrence. Dig Dis Sci. 2014;59(9):2058-68. doi: 10.1007/s10620-014-3182-7. PubMed PMID: 24795038.
• 25. Kurata M, Okajima K, Kawamoto T, Uchiba M, Ohkohchi N. Antithrombin reduces reperfusion-induced hepatic metastasis of colon cancer cells. World J Gastroenterol. 2006;12(1):60-5. doi: 10.3748/wjg.v12.i1.60. PubMed PMID: 16440418.
• 26. Nicoud IB, Jones CM, Pierce JM, Earl TM, Matrisian LM, Chari RS, et al. Warm hepatic ischemia-reperfusion promotes growth of colorectal carcinoma micrometastases in mouse liver via matrix metalloproteinase-9 induction. Cancer Res. 2007;67(6):2720-8. doi: 10.1158/0008-5472.CAN-06-3923. PubMed PMID: 17363593.
• 27. Yazdani HO, Tohme S. Murine Model of Metastatic Liver Tumors in the Setting of Ischemia Reperfusion Injury. J Vis Exp. 2019(150). Epub 2019/09/17. doi: 10.3791/59748. PubMed PMID: 31524857.
• 28. Man K, Ng KT, Lo CM, Ho JW, Sun BS, Sun CK, et al. Ischemia-reperfusion of small liver remnant promotes liver tumor growth and metastases--activation of cell invasion and migration pathways. Liver Transpl. 2007;13(12):1669-77. doi: 10.1002/lt.21193. PubMed PMID: 18044786.
• 29. Yoshimoto K, Tajima H, Ohta T, Okamoto K, Sakai S, Kinoshita J, et al. Increased E-selectin in hepatic ischemia-reperfusion injury mediates liver metastasis of pancreatic cancer. Oncol Rep. 2012;28(3):791-6. Epub 2012/07/07. doi: 10.3892/or.2012.1896. PubMed PMID: 22766603.
• 30. Noman MZ, Hasmim M, Messai Y, Terry S, Kieda C, Janji B, et al. Hypoxia: a key player in antitumor immune response. A Review in the Theme: Cellular Responses to Hypoxia. Am J Physiol Cell Physiol. 2015;309(9):C569-79. Epub 2015/08/28. doi: 10.1152/ajpcell.00207.2015. PubMed PMID: 26310815.
• 31. Crawford RS, Hashmi FF, Jones JE, Albadawi H, McCormack M, Eberlin K, et al. A novel model of acute murine hindlimb ischemia. Am J Physiol Heart Circ Physiol. 2007;292(2):H830-7. doi: 10.1152/ajpheart.00581.2006. PubMed PMID: 17012358.
• 32. Nguyen DX, Bos PD, Massague J. Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer. 2009;9(4):274-84. Epub 2009/03/25. doi: 10.1038/nrc2622. PubMed PMID: 19308067.
• 33. Diaz-Montero CM, Salem ML, Nishimura MI, Garrett-Mayer E, Cole DJ, Montero AJ. Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother. 2009;58(1):49-59. doi: 10.1007/s00262-008-0523-4. PubMed PMID: 18446337.
• 34. Van der Bilt JD, Livestro DP, Borren A, van Hillegersberg R, Borel Rinkes IH. European survey on the application of vascular clamping in liver surgery. Dig Surg. 2007;24(6):423-35. doi: 10.1159/000108325. PubMed PMID: 17855781.
• 35. Van der Bilt JD, Soeters ME, Duyverman AM, Nijkamp MW, Witteveen PO, van Diest PJ, et al. Perinecrotic hypoxia contributes to ischemia/reperfusion-accelerated outgrowth of colorectal micrometastases. Am J Pathol. 2007;170(4):1379-88. Epub 2007/03/30. doi: 10.2353/ajpath.2007.061028. PubMed PMID: 17392176.
• 36. Chen Z, Zhang P, Xu Y, Yan J, Liu Z, Lau WB, et al. Surgical stress and cancer progression: the twisted tango. Mol Cancer. 2019;18(1):132. doi: 10.1186/s12943-019-1058-3. PubMed PMID: 31477121.
• 37. Ma X, Wang M, Yin T, Zhao Y, Wei X. Myeloid-Derived Suppressor Cells Promote Metastasis in Breast Cancer After the Stress of Operative Removal of the Primary Cancer. Front Oncol. 2019;9:855. Epub 2019/09/26. doi: 10.3389/fonc.2019.00855. PubMed PMID: 31552179.
• 38. Krall JA, Reinhardt F, Mercury OA, Pattabiraman DR, Brooks MW, Dougan M, et al. The systemic response to surgery triggers the outgrowth of distant immune-controlled tumors in mouse models of dormancy. Sci Transl Med. 2018;10(436). Epub 2018/04/13. doi: 10.1126/scitranslmed.aan3464. PubMed PMID: 29643230.
• 39. Lejay A, Meyer A, Schlagowski AI, Charles AL, Singh F, Bouitbir J, et al. Mitochondria: mitochondrial participation in ischemia-reperfusion injury in skeletal muscle. Int J Biochem Cell Biol. 2014;50:101-5. doi: 10.1016/j.biocel.2014.02.013. PubMed PMID: 24582887.
• 40. Butterfield TA, Best TM, Merrick MA. The dual roles of neutrophils and macrophages in inflammation: a critical balance between tissue damage and repair. J Athl Train. 2006;41(4):457-65. PubMed PMID: 17273473.
• 41. Nagai S, Yoshida A, Facciuto M, Moonka D, Abouljoud MS, Schwartz ME, et al. Ischemia time impacts recurrence of hepatocellular carcinoma after liver transplantation. Hepatology. 2015;61(3):895-904. Epub 2014/08/08. doi: 10.1002/hep.27358. PubMed PMID: 25099130.
• 42. Orci LA, Berney T, Majno PE, Lacotte S, Oldani G, Morel P, et al. Donor characteristics and risk of hepatocellular carcinoma recurrence after liver transplantation. Br J Surg. 2015;102(10):1250-7. Epub 2015/06/23. doi: 10.1002/bjs.9868. PubMed PMID: 26098966.
• 43. Lai IR, Chang KJ, Chen CF, Tsai HW. Transient limb ischemia induces remote preconditioning in liver among rats: the protective role of heme oxygenase-1. Transplantation. 2006;81(9):1311-7. Epub 2006/05/16. doi: 10.1097/01.tp.0000203555.14546.63. PubMed PMID: 16699460.