Evaluation of Selected Circulating Cytokines from the IL-6 Family - Interleukin 6, Oncostatin M, and Cardiotrophin-1 - in Gastro-entero-pancreatic and Bronchial Neuroendocrine Tumours

Overview

Journal Contemp Oncol (Pozn)

Publisher Termedia

Specialty Oncology

Date 2024 Oct 18

PMID 39421708

Authors

Janusz Strzelczyk

Ksenia Janas

Joanna Katarzyna Strzelczyk

Elzbieta Chelmecka

Dariusz Kajdaniuk

Beata Kos-Kudla

Affiliations

Soon will be listed here.

Abstract

Introduction: The incidence of neuroendocrine tumours (NETs) increased over the last years. Most of them are non-functioning, and the course of the disease is asymptomatic for a long time. This results in late diagnosis at an advanced stage. The aim of our study was the evaluation of selected circulating cytokines of interleukin-6 family - interleukin 6 (IL-6), oncostatin M (OSM), and cardiotrophin-1 (CT1) - in NETs.

Material And Methods: The study group comprised 80 patients (56%) in several subgroups, including gastroenteropancreatic (GEPNETs, = 64, 80%) and bronchopulmonary neuroendocrine tumours (BPNETs, = 16; 20%). Serum IL-6, OSM, and CT1 concentrations were tested using ELISA.

Results: The median concentration of IL-6 was 41.5 pg/ml in the study group and 32.6 pg/ml in the control group, and the difference was statistically significant ( < 0.001). The concentration of OSM was significantly lower in the study group than in the control group ( < 0.001), at 105.6 pg/ml and 115.5 pg/ml, respectively. There was a significant difference ( < 0.01) in concentration of CT1 in the study group (222.0 pg/ml) and controls (267.2 pg/ml). Our investigation into selected IL-6 family cytokines revealed differential modulation of signal transduction pathways.

Conclusions: These findings suggest that despite utilising a common signalling transducer, individual IL-6 family cytokines exert distinct biological effects on neuroendocrine tumour development. Notably, IL-6 appears to promote tumourigenesis, while OSM and CT1 exhibit inhibitory effects on gastro-entero-pancreatic and bronchial neuroendocrine tumour development. Further studies are necessary to validate the diagnostic utility of IL-6 family cytokines in NETs.

References

Lee B, Hogg E, Below C, Kononov A, Blanco-Gomez A, Heider F . Heterocellular OSM-OSMR signalling reprograms fibroblasts to promote pancreatic cancer growth and metastasis. Nat Commun. 2021; 12(1):7336. PMC: 8683436. DOI: 10.1038/s41467-021-27607-8. View

Scoles D, Xu X, Wang H, Tran H, Taylor-Harding B, Li A . Liver X receptor agonist inhibits proliferation of ovarian carcinoma cells stimulated by oxidized low density lipoprotein. Gynecol Oncol. 2009; 116(1):109-16. DOI: 10.1016/j.ygyno.2009.09.034. View

Gibson W, Gonzalez R, Cates J, Liu E, Shi C . Hepatic micrometastases are associated with poor prognosis in patients with liver metastases from neuroendocrine tumors of the digestive tract. Hum Pathol. 2018; 79:109-115. PMC: 6133739. DOI: 10.1016/j.humpath.2018.05.006. View

Fossey S, Bear M, Kisseberth W, Pennell M, London C . Oncostatin M promotes STAT3 activation, VEGF production, and invasion in osteosarcoma cell lines. BMC Cancer. 2011; 11:125. PMC: 3079692. DOI: 10.1186/1471-2407-11-125. View

Lamano J, Lamano J, Li Y, DiDomenico J, Choy W, Veliceasa D . Glioblastoma-Derived IL6 Induces Immunosuppressive Peripheral Myeloid Cell PD-L1 and Promotes Tumor Growth. Clin Cancer Res. 2019; 25(12):3643-3657. PMC: 6571046. DOI: 10.1158/1078-0432.CCR-18-2402. View

Lopez-Andres N, Calvier L, Labat C, Fay R, Diez J, Benetos A . Absence of cardiotrophin 1 is associated with decreased age-dependent arterial stiffness and increased longevity in mice. Hypertension. 2012; 61(1):120-9. DOI: 10.1161/HYPERTENSIONAHA.112.201699. View

Geethadevi A, Nair A, Parashar D, Ku Z, Xiong W, Deng H . Oncostatin M Receptor-Targeted Antibodies Suppress STAT3 Signaling and Inhibit Ovarian Cancer Growth. Cancer Res. 2021; 81(20):5336-5352. PMC: 8530981. DOI: 10.1158/0008-5472.CAN-21-0483. View

Kos-Kudla B, Blicharz-Dorniak J, Strzelczyk J, Baldys-Waligorska A, Bednarczuk T, Bolanowski M . Diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours). Endokrynol Pol. 2017; 68(2):79-110. DOI: 10.5603/EP.2017.0015. View

Bustos M, Dubrot J, Martinez-Anso E, Larequi E, Castano D, Palazon A . Cardiotrophin-1 determines liver engraftment of syngenic colon carcinoma cells through an immune system-mediated mechanism. Oncoimmunology. 2012; 1(9):1527-1536. PMC: 3525608. DOI: 10.4161/onci.22504. View

10.

Caffarel M, Coleman N . Oncostatin M receptor is a novel therapeutic target in cervical squamous cell carcinoma. J Pathol. 2014; 232(4):386-90. PMC: 4260121. DOI: 10.1002/path.4305. View

11.

Nagtegaal I, Odze R, Klimstra D, Paradis V, Rugge M, Schirmacher P . The 2019 WHO classification of tumours of the digestive system. Histopathology. 2019; 76(2):182-188. PMC: 7003895. DOI: 10.1111/his.13975. View

12.

Konii H, Sato K, Kikuchi S, Okiyama H, Watanabe R, Hasegawa A . Stimulatory effects of cardiotrophin 1 on atherosclerosis. Hypertension. 2013; 62(5):942-50. DOI: 10.1161/HYPERTENSIONAHA.113.01653. View

13.

Lopez-Yoldi M, Moreno-Aliaga M, Bustos M . Cardiotrophin-1: A multifaceted cytokine. Cytokine Growth Factor Rev. 2015; 26(5):523-32. DOI: 10.1016/j.cytogfr.2015.07.009. View

14.

Guo Y, Xu F, Lu T, Duan Z, Zhang Z . Interleukin-6 signaling pathway in targeted therapy for cancer. Cancer Treat Rev. 2012; 38(7):904-10. DOI: 10.1016/j.ctrv.2012.04.007. View

15.

Araujo A, Abaurrea A, Azcoaga P, Lopez-Velazco J, Manzano S, Rodriguez J . Stromal oncostatin M cytokine promotes breast cancer progression by reprogramming the tumor microenvironment. J Clin Invest. 2022; 132(7). PMC: 8970678. DOI: 10.1172/JCI148667. View

16.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

17.

Zaporowska-Stachowiak I, Springer M, Stachowiak K, Oduah M, Sopata M, Wieczorowska-Tobis K . Interleukin-6 Family of Cytokines in Cancers. J Interferon Cytokine Res. 2024; 44(2):45-59. DOI: 10.1089/jir.2023.0103. View

18.

Zhang W, Liu Y, Yan Z, Yang H, Sun W, Yao Y . IL-6 promotes PD-L1 expression in monocytes and macrophages by decreasing protein tyrosine phosphatase receptor type O expression in human hepatocellular carcinoma. J Immunother Cancer. 2020; 8(1). PMC: 7319788. DOI: 10.1136/jitc-2019-000285. View

19.

Jones S, Jenkins B . Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer. Nat Rev Immunol. 2018; 18(12):773-789. DOI: 10.1038/s41577-018-0066-7. View

20.

Pavel M, Oberg K, Falconi M, Krenning E, Sundin A, Perren A . Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020; 31(7):844-860. DOI: 10.1016/j.annonc.2020.03.304. View