Toll-like receptors 2, 4 and 9 and hypoxia markers HIF-1alpha and CAIX in pancreatic intraepithelial neoplasia

Autor:	Peeter Karihtala, Tuomo J. Karttunen, Olli Helminen, Joel Isohookana, Petri Lehenkari, Joonas H. Kauppila, Seppo Parkkila, Juha Saarnio, Joni Leppänen, Heikki Huhta, Kirsi-Maria Haapasaari
Rok vydání:	2018
Předmět:	0301 basic medicine Microbiology (medical) Adult Male Carcinogenesis Pancreatic Intraepithelial Neoplasia Biology Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine Antigens Neoplasm Pancreatic cancer Neoplasms medicine Biomarkers Tumor Tumor Microenvironment Immunology and Allergy Humans Receptor Carbonic Anhydrase IX Hypoxia Pancreas Aged Retrospective Studies Inflammation Toll-like receptor TLR9 General Medicine Middle Aged medicine.disease Hypoxia-Inducible Factor 1 alpha Subunit Immunohistochemistry Immunity Innate Toll-Like Receptor 2 Gene Expression Regulation Neoplastic Pancreatic Neoplasms Toll-Like Receptor 4 TLR2 030104 developmental biology 030220 oncology & carcinogenesis Toll-Like Receptor 9 TLR4 Cancer research Female Carcinoma Pancreatic Ductal
Zdroj:	APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. 126(11)
ISSN:	1600-0463
Popis:	Pancreatic cancer arises from precursor lesions called pancreatic intraepithelial neoplasia (PanIN) characterized by inflammatory microenvironment. In pancreatic cancer, strong innate immunity and hypoxia responses are typical. Occurrence and relationship of these responses in human PanINs is unknown. We have studied the expression of toll-like receptors (TLR) TLR2, TLR4 and TLR9, and hypoxia markers HIF-1alpha and Carbonic anhydrase IX (CAIX) in normal and inflamed pancreatic ducts, in PanINs and in cancers. The samples of 69 surgically resected pancreatic ductal adenocarcinoma patients were stained using immunohistochemistry. We found TLR2, TLR9, HIF-1alpha and CAIX to be prominently expressed in pancreatic intraepithelial neoplasia. Expression of TLR2 showed a linear increase from PanIN1 to PanIN3, while the highest TLR4 expression was detected in inflamed ducts, and TLR9 expression in PanIN1 lesions. Within the PanIN1-group, nuclear HIF-1alpha correlated with membranous and cytoplasmic TLR2 expression (ρ = 0.982 and 0.815; p < 0.001 and p = 0.025, respectively), and in the PanIN2-group nuclear HIF-1alpha correlated with nuclear TLR9 expression 0.636, p = 0.026). Our findings show that the expression of TLRs 2, 4 and 9, and hypoxia markers HIF-1alpha and CAIX is abnormal in pancreatic intraepithelial neoplasia suggesting that both the innate immunity activation and hypoxia response are involved in early pancreatic carcinogenesis. However, these processes might be independent.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9eaa4fb22704d23bd24c9086ead6ddf3 https://pubmed.ncbi.nlm.nih.gov/30357962 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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