The Relationship Between Phospho-p38, Matrix Metalloproteinase 9, and Major Histocompatibility Complex Class I Chain-Related Molecule A Expression in Pituitary Adenomas Demonstrates a New Mechanism of Pituitary Adenoma Immune Escape.
World Neurosurg
; 123: e116-e124, 2019 Mar.
Article
in En
| MEDLINE
| ID: mdl-30458325
ABSTRACT
BACKGROUND:
The major histocompatibility complex class I chain-related molecule A (MICA) is one of the natural killer group 2D ligands. Soluble major histocompatibility complex class I chain-related molecule A (sMICA) mediates tumor immune escape, but the mechanism is not fully understood. In this study, we examined the expression of phospho-p38, matrix metalloproteinase 9 (MMP-9), and MICA and their relationships among each other in pituitary adenoma tissues to provide a histologic basis for the mechanism of pituitary adenoma immune escape.METHODS:
We applied immunohistochemistry, real-time quantitative reverse-transcriptase polymerase chain reaction, and Western blot to detect phospho-p38, MMP-9, and MICA expression at the mRNA and protein levels in pituitary adenoma tissues. Enzyme-linked immunosorbent assay was used to examine the expression levels of MMP-9 and sMICA in peripheral blood serum from patients with pituitary adenoma.RESULTS:
We found that p38, MICA, and MMP-9 mRNA levels were greater in pituitary adenomas than in normal tissues. The phospho-p38, MMP-9, and MICA proteins were overexpressed in pituitary adenomas, and the expression of MMP-9 and MICA were positively correlated with the expression of phospho-p38. In addition, the serum levels of sMICA and MMP-9 proteins in pituitary adenoma patients were significantly greater than those in normal controls.CONCLUSIONS:
These findings suggest that activation of the p38/mitogen-activated protein kinase pathway may increase MICA expression and induce MMP-9 expression. MMP-9 is involved in the shedding of sMICA from MICA to promote tumor immune escape. Furthermore, p38/mitogen-activated protein kinase could potentially represent a novel target for inhibiting pituitary adenoma immune escape.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pituitary Neoplasms
/
Histocompatibility Antigens Class I
/
Adenoma
/
Tumor Escape
/
Matrix Metalloproteinase 9
/
P38 Mitogen-Activated Protein Kinases
Limits:
Female
/
Humans
/
Male
Language:
En
Journal:
World Neurosurg
Journal subject:
NEUROCIRURGIA
Year:
2019
Document type:
Article
Affiliation country:
China