NOD1 and NOD2 of the innate immune system is differently expressed in human clear cell renal cell carcinoma, corresponding healthy renal tissue, its vasculature and primary isolated renal tubular epithelial cells.
Adult
Aged
Aged, 80 and over
Animals
Carcinoma, Renal Cell
/ blood supply
Epithelial Cells
/ immunology
Female
Heterografts
Humans
Immunity, Innate
Immunohistochemistry
Kidney
/ blood supply
Kidney Neoplasms
/ blood supply
Kidney Tubules
/ immunology
Male
Mice
Middle Aged
Nod1 Signaling Adaptor Protein
/ biosynthesis
Nod2 Signaling Adaptor Protein
/ biosynthesis
RNA, Messenger
/ genetics
Clear cell renal cell carcinoma
Innate immunity
Kidney cancer
NLR
Journal
Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060
Informations de publication
Date de publication:
Jun 2019
Jun 2019
Historique:
received:
22
10
2018
accepted:
19
03
2019
pubmed:
25
3
2019
medline:
14
6
2019
entrez:
24
3
2019
Statut:
ppublish
Résumé
NOD1 and NOD2 (nucleotide-binding oligomerization domain)-receptors are intracellular receptors and belong to the family of pattern recognition receptors being present in both human and murine renal tubular cells. Besides, NOD1 has been proved to promote apoptosis, upon its overexpression. Hence, we aimed to investigate NOD1 and NOD2 expression in human clear cell renal cell carcinoma (ccRCC). Tumor and corresponding adjacent healthy tissues from 41 patients with histopathological diagnosis of ccRCC as well as primary isolated renal tubular epithelial cells (TECs) and tumor tissue from a murine xenograft model using CAKI-1 ccRCC cells were analyzed. NOD1 and NOD2 mRNA was constitutively expressed in both tumor and adjacent healthy renal tissue, with NOD1 being significantly lower and in contrast NOD2 significantly higher expressed in tumor tissue compared to healthy tissues. Immunohistochemically, NOD1 was located not only in the cytoplasm, but also in the nucleus in ccRCC tissue whereas NOD2 was solely localized in the cytoplasm in both human ccRCC as well as in the healthy tubular system. Focusing on the vasculature, NOD2 displayed broader expression than NOD1. In primary TECs as well as CAKI-1 cells NOD1 and NOD2 was constitutively expressed and increasable upon LPS stimulation. In the mouse xenograft model, human NOD1 mRNA was significantly higher expressed compared to NOD2. In contrast hereto, we observed a shift towards lower mouse NOD1 compared to NOD2 mRNA expression. In view of reduced apoptosis-associated NOD1 expression in ccRCC tissue opposed to higher expression of NOD2 in tumor vasculature, inducibility of NOD expression in TECs as well as the detected shift of NOD1 and NOD2 expression in the mouse xenograft model, modulation of NOD receptors might, therefore, provide a molecular therapeutic approach in ccRCC.
Identifiants
pubmed: 30903318
doi: 10.1007/s00432-019-02901-7
pii: 10.1007/s00432-019-02901-7
doi:
Substances chimiques
NOD1 protein, human
0
NOD2 protein, human
0
Nod1 Signaling Adaptor Protein
0
Nod2 Signaling Adaptor Protein
0
RNA, Messenger
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1405-1416Subventions
Organisme : Kulemann-Stiftung
ID : non
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