Research Article
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Investigation of Calprotectin Positive Leukocytes in Canine Soft Tissue Tumors

Year 2021, Volume: 40 Issue: 2, 77 - 87, 31.12.2021
https://doi.org/10.30782/jrvm.878763

Abstract

Canine soft tissue tumors include a group of mesenchymal tumors with various tumor subtypes. Soft tissue sarcomas, on the other hand, are a complex group of tumors that are difficult to treat and have high invasion and metastasis potential. In order to determine the prognosis in malignant tumors, staging is made according to histopathological grading and metastasis features. There is information that inflammatory cell infiltrations are associated with malignancy in many human and animal tumors. Macrophages and neutrophils are found in inflammatory cells whose infiltration is observed in malignant tumor tissues. There are subtypes of both inflammatory cells, and the types associated with malignancy and poor prognosis in tumors are called tumor-associated macrophages and tumor-associated neutrophils. In this study, the presence of calprotectin positive neutrophils and macrophages in canine soft tissue tumors was investigated by immunohistochemical methods. For this purpose, mesenchymal tumors of different origins from 31 dogs of different breed, age and sex were examined. After the histopathological classification of the tumors, a comparison was made between benign and malignant tumors in terms of calprotectin positive macrophages and neutrophils. Calprotectin positivity in malignant soft tissue tumors was found to be significantly higher than benign tumors in the evaluations made on the basis of all positive cells. In the evaluations made only in terms of macrophages, a significant increase in malignant tumors was also noted. No statistically significant difference was found between benign and malignant tumors in terms of neutrophil presence. According to the results in our study, it was observed that calprotectin positive leukocyte infiltrations could be associated with malignancy in canine soft tissue tumors.

Supporting Institution

Burdur Mehmet Akif Ersoy University, Scientific Research Project Office

Project Number

0645-YL-20

Thanks

This research supported by a grant received from Burdur Mehmet Akif Ersoy University, Scientific Research Project Office (Master of Science-Project No. 0645-YL-20).

References

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  • Teng F, Tian WY, Wang YM, et al. Cancer-associated fibroblasts promote the progression of endometrial cancer via the SDF-1/CXCR4 axis. J Hematol Oncol. 2016;9(1). doi:10.1186/s13045-015-0231-4
  • Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med. 2013;19(11):1423-1437. doi:10.1038/nm.3394
  • Chen Y, Zhang S, Wang Q, Zhang X. Tumor-recruited M2 macrophages promote gastric and breast cancer metastasis via M2 macrophage-secreted CHI3L1 protein. J Hematol Oncol. 2017;10(1):1-13. doi:10.1186/s13045-017-0408-0
  • Grivennikov SI, Greten FR, Karin M. Immunity, Inflammation, and Cancer. Cell. 2010;140(6):883-899. doi:10.1016/j.cell.2010.01.025
  • Donato R. S100: A multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles. Int J Biochem Cell Biol. 2001;33(7):637-668. doi:10.1016/S1357-2725(01)00046-2
  • Heizmann CW, Fritz G, Schäfer BW. S100 proteins: structure, functions and pathology. Front Biosci. 2002;7:d1356-68. doi:10.2741/a846
  • Koy M, Hambruch N, Hussen J, Pfarrer C, Seyfert HM, Schuberth HJ. Recombinant bovine S100A8 and A9 enhance IL-1β secretion of interferon-gamma primed monocytes. Vet Immunol Immunopathol. 2013;155(3):162-170. doi:10.1016/j.vetimm.2013.07.002
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  • Monteiro LN, Rodrigues MA, Gomes DA, Salgado BS, Cassali GD. Tumour-associated macrophages: Relation with progression and invasiveness, and assessment of M1/M2 macrophages in canine mammary tumours. Vet J. 2018;234:119-125. doi:10.1016/j.tvjl.2018.02.016
  • Monteiro LN, dos Reis DC, Salgado BS, Cassali GD. Clinical significance and prognostic role of tumor-associated macrophages infiltration according to histologic location in canine mammary carcinomas. Res Vet Sci. October 2020. doi:10.1016/j.rvsc.2020.10.010
  • Woldemeskel M, Hawkins I, Whittington L. Ki-67 protein expression and tumor associated inflammatory cells (macrophages and mast cells) in canine colorectal carcinoma. BMC Vet Res. 2017;13(1). doi:10.1186/s12917-017-1030-7
  • Pires I, Prada J, Coelho L, Garcia A, Luisa F. Tumour-Associated Macrophages (TAMs) and Cox-2 Expression in Canine Melanocytic Lesions. In: Murph M, ed. Melanoma in the Clinic - Diagnosis, Management and Complications of Malignancy. Rijeka, Croatia: InTech; 2011:163-180.
  • Ichikawa M, Williams R, Wang L, Vogl T, Srikrishna G. S100A8/A9 activate key genes and pathways in colon tumor progression. Mol Cancer Res. 2011;9(2):133-148. doi:10.1158/1541-7786.MCR-10-0394
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  • Fridlender ZG, Sun J, Kim S, et al. Polarization of Tumor-Associated Neutrophil Phenotype by TGF-β: “N1” versus “N2” TAN. Cancer Cell. 2009;16(3):183-194. doi:10.1016/j.ccr.2009.06.017
  • Coffelt SB, Kersten K, Doornebal CW, et al. IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis. Nature. 2015;522(7556):345-348. doi:10.1038/nature14282
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  • Kuang DM, Zhao Q, Wu Y, et al. Peritumoral neutrophils link inflammatory response to disease progression by fostering angiogenesis in hepatocellular carcinoma. J Hepatol. 2011;54(5):948-955. doi:10.1016/j.jhep.2010.08.041
  • Rao H-L, Chen J-W, Li M, et al. Increased Intratumoral Neutrophil in Colorectal Carcinomas Correlates Closely with Malignant Phenotype and Predicts Patients’ Adverse Prognosis. Hold GL, ed. PLoS One. 2012;7(1):e30806. doi:10.1371/journal.pone.0030806
  • Trellakis S, Bruderek K, Dumitru CA, et al. Polymorphonuclear granulocytes in human head and neck cancer: Enhanced inflammatory activity, modulation by cancer cells and expansion in advanced disease. Int J Cancer. 2011;129(9):2183-2193. doi:10.1002/ijc.25892
  • Wislez M, Rabbe N, Marchal J, et al. Hepatocyte growth factor production by neutrophils infiltrating bronchioloalveolar subtype pulmonary adenocarcinoma: Role in tumor progression and death. Cancer Res. 2003;63(6):1405-1412.
  • Caruso RA, Bellocco R, Pagano M, Bertoli G, Rigoli L, Inferrera C. Prognostic value of intratumoral neutrophils in advanced gastric carcinoma in a high-risk area in Northern Italy. Mod Pathol. 2002;15(8):831-837. doi:10.1097/01.MP.0000020391.98998.6B
  • Prame Kumar K, Nicholls AJ, Wong CHY. Partners in crime: neutrophils and monocytes/macrophages in inflammation and disease. Cell Tissue Res. 2018;371(3):551-565. doi:10.1007/s00441-017-2753-2
  • Daley JM, Thomay AA, Connolly MD, Reichner JS, Albina JE. Use of Ly6G-specific monoclonal antibody to deplete neutrophils in mice. J Leukoc Biol. 2008;83(1):64-70. doi:10.1189/jlb.0407247
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Year 2021, Volume: 40 Issue: 2, 77 - 87, 31.12.2021
https://doi.org/10.30782/jrvm.878763

Abstract

Project Number

0645-YL-20

References

  • Meuten DJ. Tumors in Domestic Animals. 4th ed. Iowa: Iowa State Press; 2002. doi:10.1139/W07-062
  • Bray J. Soft tissue sarcoma in the dog: An update. In Pract. 2018;40(9):383-395. doi:10.1136/inp.k707
  • Tu Z, Xiao R, Xiong J, et al. CCR9 in cancer: Oncogenic role and therapeutic targeting. J Hematol Oncol. 2016;9(1). doi:10.1186/s13045-016-0236-7
  • Caso G, Barry C, Patejunas G. Dysregulation of CXCL9 and reduced tumor growth in Egr-1 deficient Mice. J Hematol Oncol. 2009;2(1):7. doi:10.1186/1756-8722-2-7
  • Teng F, Tian WY, Wang YM, et al. Cancer-associated fibroblasts promote the progression of endometrial cancer via the SDF-1/CXCR4 axis. J Hematol Oncol. 2016;9(1). doi:10.1186/s13045-015-0231-4
  • Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med. 2013;19(11):1423-1437. doi:10.1038/nm.3394
  • Chen Y, Zhang S, Wang Q, Zhang X. Tumor-recruited M2 macrophages promote gastric and breast cancer metastasis via M2 macrophage-secreted CHI3L1 protein. J Hematol Oncol. 2017;10(1):1-13. doi:10.1186/s13045-017-0408-0
  • Grivennikov SI, Greten FR, Karin M. Immunity, Inflammation, and Cancer. Cell. 2010;140(6):883-899. doi:10.1016/j.cell.2010.01.025
  • Donato R. S100: A multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles. Int J Biochem Cell Biol. 2001;33(7):637-668. doi:10.1016/S1357-2725(01)00046-2
  • Heizmann CW, Fritz G, Schäfer BW. S100 proteins: structure, functions and pathology. Front Biosci. 2002;7:d1356-68. doi:10.2741/a846
  • Koy M, Hambruch N, Hussen J, Pfarrer C, Seyfert HM, Schuberth HJ. Recombinant bovine S100A8 and A9 enhance IL-1β secretion of interferon-gamma primed monocytes. Vet Immunol Immunopathol. 2013;155(3):162-170. doi:10.1016/j.vetimm.2013.07.002
  • Loser K, Vogl T, Voskort M, et al. The toll-like receptor 4 ligands Mrp8 and Mrp14 are crucial in the development of autoreactive CD8+ T cells. Nat Med. 2010;16(6):713-717. doi:10.1038/nm.2150
  • Chen H, Xu C, Jin Q, Liu Z. S100 protein family in human cancer. Am J Cancer Res. 2014;4(2):89-115. http://www.ncbi.nlm.nih.gov/pubmed/24660101. Accessed January 9, 2021.
  • Balkwill F, Mantovani A. Inflammation and cancer: Back to Virchow? Lancet. 2001;357(9255):539-545. doi:10.1016/S0140-6736(00)04046-0
  • Kang JH, Hwang SM, Chung IY. S100A8, S100A9 and S100A12 activate airway epithelial cells to produce MUC5AC via extracellular signal-regulated kinase and nuclear factor-κB pathways. Immunology. 2015;144(1):79-90. doi:10.1111/imm.12352
  • Hendrick M, Mahaffeey E, Moore F, Vos J, Walder E. Histological Classification of Mesenchymal Tumors of Skin and Soft Tissues of Domestic Animals, Vol. 2. Washington DC: Armed Forces Institute of Pathology; 1998.
  • Avallone G, Helmbold P, Caniatti M, Stefanello D, Nayak RC, Roccabianca P. The spectrum of canine cutaneous perivascular wall tumors: morphologic, phenotypic and clinical characterization. Vet Pathol. 2007;44(5):607-620. doi:10.1354/vp.44-5-607
  • Gross T, Ihrke P, Walder E, Affolter V. Skin Diseases of the Dog and Cat: Clinical and Histopathologic Diagnosis. 2nd ed. Oxford: Blackwell; 2005.
  • Parkin D, Pisani P, Munoz N, Ferlay J. Infections and human cancer. In: Newton R, Beral V, Weiss R, eds. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press; 1999.
  • Gulumian M. The role of oxidative stress in diseases caused by mineral dusts and fibres: Current status and future of prophylaxis and treatment. Mol Cell Biochem. 1999;196(1-2):69-77. doi:10.1023/A:1006918212866
  • Ekbom A, Helmick C, Zack M, Adami H. Ulcerative colitis and colorectal cancer. A population-based study. New Engl J Med. 1990;323(18):1228-1233.
  • Brooks J. Disorders of soft tissue. In: Sternberg S, ed. Diagnostic Surgical Pathology. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 1999:131-221.
  • Middleton LP, Duray PH, Merino MJ. The histological spectrum of hemangiopericytoma: Application of immunohistochemical analysis including proliferative markers to facilitate diagnosis and predict prognosis. Hum Pathol. 1998;29(6):636-640. doi:10.1016/S0046-8177(98)80015-4
  • Perry A, Scheithauer BW, Nascimento AG. The immunophenotypic spectrum of meningeal hemangiopericytoma: A comparison with fibrous meningioma and solitary fibrous tumor of meninges. Am J Surg Pathol. 1997;21(11):1354-1360. doi:10.1097/00000478-199711000-00010
  • Rosai J. Soft Tissues. In: Rosai J, ed. Ackerman’s Surgical Pathology. 8th ed. St. Louis: Mosby; 1996:2021-2034.
  • Mantovani A, Bussolino F, Dejana E. Cytokine regulation of endothelial cell function. FASEB J. 1992;6(8):2591-2599. doi:10.1096/fasebj.6.8.1592209
  • Coussens LM, Tinkle CL, Hanahan D, Werb Z. MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell. 2000;103(3):481-490. doi:10.1016/S0092-8674(00)00139-2
  • Lee CH, Espinosa I, Vrijaldenhoven S, et al. Prognostic significance of macrophage infiltration in leiomyosarcomas. Clin Cancer Res. 2008;14(5):1423-1430. doi:10.1158/1078-0432.CCR-07-1712
  • Bingle L, Brown NJ, Lewis CE. The role of tumour-associated macrophages in tumour progression: Implications for new anticancer therapies. J Pathol. 2002;196(3):254-265. doi:10.1002/path.1027
  • Qian BZ, Pollard JW. Macrophage Diversity Enhances Tumor Progression and Metastasis. Cell. 2010;141(1):39-51. doi:10.1016/j.cell.2010.03.014
  • Raposo T, Gregório H, Pires I, Prada J, Queiroga FL. Prognostic value of tumour-associated macrophages in canine mammary tumours. Vet Comp Oncol. 2014;12(1):10-19. doi:10.1111/j.1476-5829.2012.00326.x
  • Monteiro LN, Rodrigues MA, Gomes DA, Salgado BS, Cassali GD. Tumour-associated macrophages: Relation with progression and invasiveness, and assessment of M1/M2 macrophages in canine mammary tumours. Vet J. 2018;234:119-125. doi:10.1016/j.tvjl.2018.02.016
  • Monteiro LN, dos Reis DC, Salgado BS, Cassali GD. Clinical significance and prognostic role of tumor-associated macrophages infiltration according to histologic location in canine mammary carcinomas. Res Vet Sci. October 2020. doi:10.1016/j.rvsc.2020.10.010
  • Woldemeskel M, Hawkins I, Whittington L. Ki-67 protein expression and tumor associated inflammatory cells (macrophages and mast cells) in canine colorectal carcinoma. BMC Vet Res. 2017;13(1). doi:10.1186/s12917-017-1030-7
  • Pires I, Prada J, Coelho L, Garcia A, Luisa F. Tumour-Associated Macrophages (TAMs) and Cox-2 Expression in Canine Melanocytic Lesions. In: Murph M, ed. Melanoma in the Clinic - Diagnosis, Management and Complications of Malignancy. Rijeka, Croatia: InTech; 2011:163-180.
  • Ichikawa M, Williams R, Wang L, Vogl T, Srikrishna G. S100A8/A9 activate key genes and pathways in colon tumor progression. Mol Cancer Res. 2011;9(2):133-148. doi:10.1158/1541-7786.MCR-10-0394
  • Zhong JM, Li J, Kang AD, et al. Protein S100-A8: A potential metastasis-associated protein for breast cancer determined via iTRAQ quantitative proteomic and clinicopathological analysis. Oncol Lett. 2018;15(4):5285-5293. doi:10.3892/ol.2018.7958
  • Srikrishna G. S100A8 and S100A9: New insights into their roles in malignancy. J Innate Immun. 2011;4(1):31-40. doi:10.1159/000330095
  • Rajendran P, Chen YF, Chen YF, et al. The multifaceted link between inflammation and human diseases. J Cell Physiol. 2018;233(9):6458-6471. doi:10.1002/jcp.26479
  • Leliefeld PHC, Koenderman L, Pillay J. How neutrophils shape adaptive immune responses. Front Immunol. 2015;6(SEP). doi:10.3389/fimmu.2015.00471
  • Negus RPM, Stamp GWH, Hadley J, Balkwill FR. Quantitative assessment of the leukocyte infiltrate in ovarian cancer and its relationship to the expression of C-C chemokines. Am J Pathol. 1997;150(5):1723-1734. /pmc/articles/PMC1858213/?report=abstract. Accessed January 12, 2021.
  • Fridlender ZG, Sun J, Kim S, et al. Polarization of Tumor-Associated Neutrophil Phenotype by TGF-β: “N1” versus “N2” TAN. Cancer Cell. 2009;16(3):183-194. doi:10.1016/j.ccr.2009.06.017
  • Coffelt SB, Kersten K, Doornebal CW, et al. IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis. Nature. 2015;522(7556):345-348. doi:10.1038/nature14282
  • Brandau S, Dumitru CA, Lang S. Protumor and antitumor functions of neutrophil granulocytes. Semin Immunopathol. 2013;35(2):163-176. doi:10.1007/s00281-012-0344-6
  • Jensen HK, Donskov F, Marcussen N, Nordsmark M, Lundbeck F, Von Der Maase H. Presence of intratumoral neutrophils is an independent prognostic factor in localized renal cell carcinoma. J Clin Oncol. 2009;27(28):4709-4717. doi:10.1200/JCO.2008.18.9498
  • Kuang DM, Zhao Q, Wu Y, et al. Peritumoral neutrophils link inflammatory response to disease progression by fostering angiogenesis in hepatocellular carcinoma. J Hepatol. 2011;54(5):948-955. doi:10.1016/j.jhep.2010.08.041
  • Rao H-L, Chen J-W, Li M, et al. Increased Intratumoral Neutrophil in Colorectal Carcinomas Correlates Closely with Malignant Phenotype and Predicts Patients’ Adverse Prognosis. Hold GL, ed. PLoS One. 2012;7(1):e30806. doi:10.1371/journal.pone.0030806
  • Trellakis S, Bruderek K, Dumitru CA, et al. Polymorphonuclear granulocytes in human head and neck cancer: Enhanced inflammatory activity, modulation by cancer cells and expansion in advanced disease. Int J Cancer. 2011;129(9):2183-2193. doi:10.1002/ijc.25892
  • Wislez M, Rabbe N, Marchal J, et al. Hepatocyte growth factor production by neutrophils infiltrating bronchioloalveolar subtype pulmonary adenocarcinoma: Role in tumor progression and death. Cancer Res. 2003;63(6):1405-1412.
  • Caruso RA, Bellocco R, Pagano M, Bertoli G, Rigoli L, Inferrera C. Prognostic value of intratumoral neutrophils in advanced gastric carcinoma in a high-risk area in Northern Italy. Mod Pathol. 2002;15(8):831-837. doi:10.1097/01.MP.0000020391.98998.6B
  • Prame Kumar K, Nicholls AJ, Wong CHY. Partners in crime: neutrophils and monocytes/macrophages in inflammation and disease. Cell Tissue Res. 2018;371(3):551-565. doi:10.1007/s00441-017-2753-2
  • Daley JM, Thomay AA, Connolly MD, Reichner JS, Albina JE. Use of Ly6G-specific monoclonal antibody to deplete neutrophils in mice. J Leukoc Biol. 2008;83(1):64-70. doi:10.1189/jlb.0407247
  • Nauseef WM. How human neutrophils kill and degrade microbes: An integrated view. Immunol Rev. 2007;219(1):88-102. doi:10.1111/j.1600-065X.2007.00550.x
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There are 61 citations in total.

Details

Primary Language English
Subjects Veterinary Surgery
Journal Section Research Articles
Authors

Onur Savaş 0000-0001-9159-5182

Volkan İpek 0000-0001-5874-7797

Project Number 0645-YL-20
Publication Date December 31, 2021
Acceptance Date August 4, 2021
Published in Issue Year 2021 Volume: 40 Issue: 2

Cite

APA Savaş, O., & İpek, V. (2021). Investigation of Calprotectin Positive Leukocytes in Canine Soft Tissue Tumors. Journal of Research in Veterinary Medicine, 40(2), 77-87. https://doi.org/10.30782/jrvm.878763
AMA Savaş O, İpek V. Investigation of Calprotectin Positive Leukocytes in Canine Soft Tissue Tumors. J Res Vet Med. December 2021;40(2):77-87. doi:10.30782/jrvm.878763
Chicago Savaş, Onur, and Volkan İpek. “Investigation of Calprotectin Positive Leukocytes in Canine Soft Tissue Tumors”. Journal of Research in Veterinary Medicine 40, no. 2 (December 2021): 77-87. https://doi.org/10.30782/jrvm.878763.
EndNote Savaş O, İpek V (December 1, 2021) Investigation of Calprotectin Positive Leukocytes in Canine Soft Tissue Tumors. Journal of Research in Veterinary Medicine 40 2 77–87.
IEEE O. Savaş and V. İpek, “Investigation of Calprotectin Positive Leukocytes in Canine Soft Tissue Tumors”, J Res Vet Med, vol. 40, no. 2, pp. 77–87, 2021, doi: 10.30782/jrvm.878763.
ISNAD Savaş, Onur - İpek, Volkan. “Investigation of Calprotectin Positive Leukocytes in Canine Soft Tissue Tumors”. Journal of Research in Veterinary Medicine 40/2 (December 2021), 77-87. https://doi.org/10.30782/jrvm.878763.
JAMA Savaş O, İpek V. Investigation of Calprotectin Positive Leukocytes in Canine Soft Tissue Tumors. J Res Vet Med. 2021;40:77–87.
MLA Savaş, Onur and Volkan İpek. “Investigation of Calprotectin Positive Leukocytes in Canine Soft Tissue Tumors”. Journal of Research in Veterinary Medicine, vol. 40, no. 2, 2021, pp. 77-87, doi:10.30782/jrvm.878763.
Vancouver Savaş O, İpek V. Investigation of Calprotectin Positive Leukocytes in Canine Soft Tissue Tumors. J Res Vet Med. 2021;40(2):77-8.