IL-32 expression associated with lymph vessel invasion in intestinal type of gastric cancer

Mladen Pavlović; Milena Jurišević; Nevena Gajović; Slobodanka Mitrović; Milan Jovanović; Gordana Radosavljević; Jelena Pantić; Dragče  Radovanović; Nebojša  Arsenijević; Ivan Jovanović

doi:10.2298/VSP180727158P

Mladen Pavlović University of Kragujevac, Faculty of Medical Sciences, Department of Surgery, Kragujevac, Serbia
Milena Jurišević University of Kragujevac, Faculty of Medical Sciences, Department of Pharmacy, Kragujevac, Serbia
Nevena Gajović University of Kragujevac, Faculty of Medical Sciences, Center for Molecular Medicine and Stem Cell Research , Kragujevac, Serbia
Slobodanka Mitrović University of Kragujevac, Faculty of Medical Sciences, Department of Pathology, Kragujevac, Serbia
Milan Jovanović Military Medical Academy, Department of Abdominal Surgery, Belgrade, Serbia
Gordana Radosavljević University of Kragujevac, Faculty of Medical Sciences, Center for Molecular Medicine and Stem Cell Research, Kragujevac, Serbia
Jelena Pantić University of Kragujevac, Faculty of Medical Sciences, Center for Molecular Medicine and Stem Cell Research, Kragujevac, Serbia
Dragče Radovanović University of Kragujevac, Faculty of Medical Sciences, Department of Surgery, Kragujevac, Serbia
Nebojša Arsenijević University of Kragujevac, Faculty of Medical Sciences, Center for Molecular Medicine and Stem Cell Research, Kragujevac, Serbia
Ivan Jovanović University of Kragujevac, Faculty of Medical Sciences, Center for Molecular Medicine and Stem Cell Research, Kragujevac, Serbia

DOI: https://doi.org/10.2298/VSP180727158P

Keywords: stomach neoplasms, il 32 protein, human, anti-allergic agents, severity of illness index, vascular endothelial growth factors, immunohistochemistry

Abstract

Background/Aim. Gastric cancer (GC) is fourth most frequent malignant tumor worldwide, frequently diagnosed at advanced stages with poor prognosis. The aim of study was to determine expression of interleukin (IL)-32, pro-inflammatory and angiogenic mediators in the tumor, peritumor and healthy tissue, in patients with intestinal gastric cancer and the relationship with the disease severity. Methods. The tissue samples of intestinal type of the tumor of 60 patients with GC were analyzed. Expression of IL-32, vascular endothelial growth factor (VEGF), IL-17 and CD31 were measured by immunohistochemistry. Results. IL-32, VEGF and IL-17 expression as well as microvascular density (MVD) were diminished in adjacent tumor tissues compared with the tumor ones. Further, more intense expression of IL-32 and VEGF and enhanced MVD were noticed in patients with severe (TNM stages III and IV) and more progressive GC (lymph vessel invasion). Conclusion. Higher expression of IL-32, VEGF and intense MVD in the tumor tissue of GC patients with detectable lymph vessel invasion may be considered as a sign of the tumor’s malignant progression. This indicates a protumorogenic and proangiogenic role of IL-32 in biology of intestinal type of gastric cancer.

References

Ang TL, Fock KM. Clinical epidemiology of gastric cancer. Singapore Med J 2014; 55(12): 621–8.

Lauren P. The two histological main types of gastric carcino-ma: Diffuse and so-called intestinal-type carcinoma. An at-tempt at a histo-clinical classification. Acta Pathol Microbiol Scand 1965; 64: 31–49.

Yaghoobi M, Bijarchi R, Narod SA. Family history and the risk of gastric cancer. Br J Cancer 2010; 102(2): 237–42.

Correa P, Houghton J. Carcinogenesis of Helicobacter pylori. Gastroenterology 2007; 133(2): 659–72.

Correa P. Gastric cancer: overview. Gastroenterol Clin North Am 2013; 42(2): 211–7.

Bondar’ VG, Saliev IA, Ostapenko GV, Bondar’ GV. Late diag-nosis, complications and treatment of gastric cancer. Klin Khir 2006; (3): 8–13. (Bulgarian)

Joosten LA, Heinhuis B, Netea MG, Dinarello CA. Novel in-sights into the biology of interleukin-32. Cell Mol Life Sci 2013; 70(20): 3883–92.

Kim S. Interleukin-32 in inflammatory autoimmune diseases. Immune Netw 2014; 14(3): 123–7.

Choi J Da, Bae SY, Hong JW, Azam T, Dinarello CA, Her E, et al. Identification of the most active interleukin-32 isoform. Immunology 2009; 126(4): 535–42.

Kobayashi H, Lin PC. Molecular characterization of IL-32 in human endothelial cells. Cytokine 2009; 46(3): 351–8.

Hong JT, Son DJ, Lee CK, Yoon DY, Lee DH, Park MH. Inter-leukin 32, inflammation and cancer. Pharmacol Ther 2017; 174: 127–37.

Hu LJ, Li L, Fitzpatrick JE, Francis SO, Fujita M, Takashi MK, et al. The Proinflammatory Cytokine Interleukin-32 is ex-pressed in Keratinocytes and Dendritic Cells Obtained from Patients with Chronic Plaque Psoriasis (CPPs). J Immunol 2007; 178(Meeting Abstracts): S165.

Joosten LA, Netea MG, Kim SH, Yoon DY, Oppers-Walgreen B, Radstake TR, et al. IL-32, a proinflammatory cytokine in rheumatoid arthritis. Proc Natl Acad Sci U S A 2006; 103(9): 3298–303.

Nold-Petry CA, Rudloff I, Baumer Y, Ruvo M, Marasco D, Botti P, et al. IL-32 promotes angiogenesis. J Immunol 2014; 192(2): 589–602.

Yang Y, Wang Z, Zhou Y, Wang X, Xiang J, Chen Z. Dysregula-tion of over-expressed IL-32 in colorectal cancer induces me-tastasis. World J Surg Oncol 2015; 13: 146.

Smith AJ, Toledo CM, Wietgrefe SW, Duan L, Schacker TW, Reil-ly CS, et al. The immunosuppressive role of IL-32 in lymphat-ic tissue during HIV-1 infection. J Immunol 2011; 186(11): 6576–84.

Yun J, Park MH, Son DJ, Nam KT, Moon DB, Ju JH, et al. IL-32 gamma reduces lung tumor development through upregula-tion of TIMP-3 overexpression and hypomethylation. Cell Death Dis 2018; 9(3): 306.

Yousif NG, Al-Amran FG, Hadi N, Lee J, Adrienne J. Expres-sion of IL-32 modulates NF-kappaB and p38 MAP kinase pathways in human esophageal cancer. Cytokine 2013; 61(1): 223–7.

Raica M, Mogoantă L, Cîmpean AM, Alexa A, Ioanovici S, Mărgăritescu C, et al. Immunohistochemical expression of vas-cular endothelial growth factor (VEGF) in intestinal type gas-tric carcinoma. Rom J Morphol Embryol 2008; 49(1): 37–42.

Lastraioli E, Boni L, Romoli MR, Crescioli S, Taddei A, Beghelli S, et al. VEGF-A clinical significance in gastric cancers: Im-munohistochemical analysis of a wide Italian cohort. Eur J Surg Oncol 2014; 40(10): 1291–8.

Iida T, Iwahashi M, Katsuda M, Ishida K, Nakamori M, Nakamu-ra M, et al. Tumor-infiltrating CD4+ Th17 cells produce IL-17 in tumor microenvironment and promote tumor progres-sion in human gastric cancer. Oncol Rep 2011; 25(5): 1271–7.

Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLO-BOCAN 2008. Int J Cancer 2010; 127(12): 2893–917.

Bray F, Ren JS, Masuyer E, Ferlay J. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer 2013; 132(5): 1133–45.

Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomarkers Prev 2014; 23(5): 700–13.

Ma J, Shen H, Kapesa L, Zeng S. Lauren classification and indi-vidualized chemotherapy in gastric cancer. Oncol Lett 2016; 11(5): 2959–64.

Hu B, El Hajj N, Sittler S, Lammert N, Barnes R, Meloni-Ehrig A. Gastric cancer: Classification, histology and application of molecular pathology. J Gastrointest Oncol 2012; 3(3): 251–61.

Zhou Y, Zhu Y. Important Role of the IL-32 Inflammatory Network in the Host Response against Viral Infection. Viruses 2015; 7(6): 3116–29.

Kim KH, Shim JH, Seo EH, Cho MC, Kang JW, Kim SH, et al. Interleukin-32 monoclonal antibodies for Immunohistochem-istry, Western blotting, and ELISA. J Immunol Methods 2008; 333(1–2): 38–50.

Seo EH, Kang J, Kim KH, Cho MC, Lee S, Kim HJ, et al. Detec-tion of expressed IL-32 in human stomach cancer using ELI-SA and immunostaining. J Microbiol Biotechnol 2008; 18(9): 1606–12.

Wang YM, Li ZX, Tang FB, Zhang Y, Zhou T, Zhang L, et al. Association of genetic polymorphisms of interleukins with gas-tric cancer and precancerous gastric lesions in a high-risk Chi-nese population. Tumor Biol 2016; 37(2): 2233–42.

Tsai CY, Wang CS, Tsai MM, Chi HC, Cheng WL, Tseng YH, et al. Interleukin-32 increases human gastric cancer cell inva-sion associated with tumor progression and metastasis. Clin Cancer Res 2014; 20(9): 2276–88.

Sennino B, Kuhnert F, Tabruyn SP, Mancuso MR, Hu-Lowe DD, Kuo CJ, et al. Cellular source and amount of vascular endothe-lial growth factor and platelet-derived growth factor in tumors determine response to angiogenesis inhibitors. Cancer Res 2009; 69(10): 4527–36.

Lertkiatmongkol P, Liao D, Mei H, Hu Y, Newman PJ. Endothe-lial functions of platelet/endothelial cell adhesion molecule-1 (CD31). Curr Opin Hematol 2016; 23(3): 253–9.

Privratsky JR, Newman PJ. PECAM-1: regulator of endothelial junctional integrity. Cell Tissue Res 2014; 355(3): 607–19.

Zhao HC, Qin R, Chen XX, Sheng X, Wu JF, Wang DB, et al. Microvessel density is a prognostic marker of human gastric cancer. World J Gastroenterol 2006; 12(47): 7598–603.

Niki T, Iba S, Tokunou M, Yamada T, Matsuno Y, Hirohashi S. Expression of vascular endothelial growth factors A, B, C, and D and their relationships to lymph node status in lung adeno-carcinoma. Clin Cancer Res 2000; 6(6): 2431–9.

Bo W, Yang T, Huan T, Shi-Lei W, Shi-Hang T, Hui H, et al. Correlations between VEGF-A expression and prognosis in patients with gastric adenocarcinoma. Int J Clin Exp Pathol 2017; 10(8): 8461–9

Fabre J, Giustiniani J, Garbar C, Antonicelli F, Merrouche Y, Bensussan A, et al. Targeting the Tumor Microenvironment: The Protumor Effects of IL-17 Related to Cancer Type. Int J Mol Sci 2016; 17(9): pii: E1433.

Zhu XD, Zhang JB, Zhuang PY, Zhu HG, Zhang W, Xiong YQ, et al. High expression of macrophage colony-stimulating factor in peritumoral liver tissue is associated with poor survival af-ter curative resection of hepatocellular carcinoma. J Clin On-col 2008; 26(16): 2707–16.

Tzoutzos K, Batistatou A, Kitsos G, Liasko R, Stefanou D. Study of microvascular density and expression of vascular endotheli-al growth factor and its receptors in cancerous and precancer-ous lesions of the eyelids. Anticancer Res 2014; 34(9): 4977–83.

Zhuang PY, Shen J, Zhu XD, Lu L, Wang L, Tang ZY, et al. Prognostic Roles of Cross-Talk between Peritumoral Hepato-cytes and Stromal Cells in Hepatocellular Carcinoma Involv-ing Peritumoral VEGF-C, VEGFR-1 and VEGFR-3. Sarkar D, editor. PLoS One 2013; 8(5): e64598.

Asukai K, Kawamoto K, Eguchi H, Konno M, Nishida N, Koseki J, et al. Prognostic Impact of Peritumoral IL-17-Positive Cells and IL-17 Axis in Patients with Intrahepatic Cholangiocarci-noma. Ann Surg Oncol 2015; 22 Suppl 3: S1524–31.