TRAIL receptors promote constitutive and inducible IL-8 secretion in non-small cell lung carcinoma.

Autor: Favaro F; Preclinical and Experimental Research in Thoracic Tumors (PReTT), Molecular Mechanisms and Experimental Therapy in Oncology Program (Oncobell), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, 08908, Barcelona, Spain.; Amsterdam UMC location University of Amsterdam, Department of Experimental Immunology, Meibergdreef 9, Amsterdam, The Netherlands., Luciano-Mateo F; Preclinical and Experimental Research in Thoracic Tumors (PReTT), Molecular Mechanisms and Experimental Therapy in Oncology Program (Oncobell), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, 08908, Barcelona, Spain., Moreno-Caceres J; Preclinical and Experimental Research in Thoracic Tumors (PReTT), Molecular Mechanisms and Experimental Therapy in Oncology Program (Oncobell), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, 08908, Barcelona, Spain., Hernández-Madrigal M; Preclinical and Experimental Research in Thoracic Tumors (PReTT), Molecular Mechanisms and Experimental Therapy in Oncology Program (Oncobell), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, 08908, Barcelona, Spain., Both D; Preclinical and Experimental Research in Thoracic Tumors (PReTT), Molecular Mechanisms and Experimental Therapy in Oncology Program (Oncobell), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, 08908, Barcelona, Spain.; Amsterdam UMC location University of Amsterdam, Department of Experimental Immunology, Meibergdreef 9, Amsterdam, The Netherlands., Montironi C; Amsterdam UMC location University of Amsterdam, Department of Experimental Immunology, Meibergdreef 9, Amsterdam, The Netherlands., Püschel F; Preclinical and Experimental Research in Thoracic Tumors (PReTT), Molecular Mechanisms and Experimental Therapy in Oncology Program (Oncobell), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, 08908, Barcelona, Spain., Nadal E; Preclinical and Experimental Research in Thoracic Tumors (PReTT), Molecular Mechanisms and Experimental Therapy in Oncology Program (Oncobell), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, 08908, Barcelona, Spain.; Thoracic Oncology Unit, Department of Medical Oncology, Institut Català d'Oncologia (ICO), L'Hospitalet de Llobregat, 08908, Barcelona, Spain., Eldering E; Amsterdam UMC location University of Amsterdam, Department of Experimental Immunology, Meibergdreef 9, Amsterdam, The Netherlands.; Amsterdam Institute for Infection and Immunity, Cancer Immunology, Amsterdam, The Netherlands.; Cancer Center Amsterdam, Cancer Biology, Amsterdam, The Netherlands., Muñoz-Pinedo C; Preclinical and Experimental Research in Thoracic Tumors (PReTT), Molecular Mechanisms and Experimental Therapy in Oncology Program (Oncobell), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, 08908, Barcelona, Spain. cmunoz@idibell.cat.
Jazyk: angličtina
Zdroj: Cell death & disease [Cell Death Dis] 2022 Dec 15; Vol. 13 (12), pp. 1046. Date of Electronic Publication: 2022 Dec 15.
DOI: 10.1038/s41419-022-05495-0
Abstrakt: Interleukin-8 (IL-8/CXCL8) is a pro-angiogenic and pro-inflammatory chemokine that plays a role in cancer development. Non-small cell lung carcinoma (NSCLC) produces high amounts of IL-8, which is associated with poor prognosis and resistance to chemo-radio and immunotherapy. However, the signaling pathways that lead to IL-8 production in NSCLC are unresolved. Here, we show that expression and release of IL-8 are regulated autonomously by TRAIL death receptors in several squamous and adenocarcinoma NSCLC cell lines. NSCLC constitutively secrete IL-8, which could be further enhanced by glucose withdrawal or by treatment with TRAIL or TNFα. In A549 cells, constitutive and inducible IL-8 production was dependent on NF-κB and MEK/ERK MAP Kinases. DR4 and DR5, known regulators of these signaling pathways, participated in constitutive and glucose deprivation-induced IL-8 secretion. These receptors were mainly located intracellularly. While DR4 signaled through the NF-κB pathway, DR4 and DR5 both regulated the ERK-MAPK and Akt pathways. FADD, caspase-8, RIPK1, and TRADD also regulated IL-8. Analysis of mRNA expression data from patients indicated that IL-8 transcripts correlated with TRAIL, DR4, and DR5 expression levels. Furthermore, TRAIL receptor expression levels also correlated with markers of angiogenesis and neutrophil infiltration in lung squamous carcinoma and adenocarcinoma. Collectively, these data suggest that TRAIL receptor signaling contributes to a pro-tumorigenic inflammatory signature associated with NSCLC.
(© 2022. The Author(s).)
Databáze: MEDLINE
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