Back to Search
Start Over
Sulfatase 2 Affects Polarization of M2 Macrophages through the IL-8/JAK2/STAT3 Pathway in Bladder Cancer.
- Source :
- Cancers; Jan2023, Vol. 15 Issue 1, p131, 17p
- Publication Year :
- 2023
-
Abstract
- Simple Summary: At present, the immunotherapy and immune microenvironment of bladder cancer have attracted more and more attention from clinicians and researchers. In this study, the high expression of SULF2 by RNA sequencing of tissues from 90 bladder cancer patients was associated with poor prognosis in patients. We further found that a high expression of SULF2 can promote the polarization of macrophages to M2. In mechanistic studies, we found that SULF2 can promote the secretion of IL-8 through Wnt/β-catenin. IL-8 promotes the transcription of CD163 and CD206 in the microenvironment, ultimately leading to the polarization of macrophages to M2 macrophages. This study elucidates the effect of SULF2 on the polarization of macrophages in the tumor microenvironment. Sulfatase 2 (SULF2) affects the occurrence and development of cancer by regulating HSPG-binding factors. However, the mechanism of SULF2 in bladder cancer (BCa) is unknown. To determine this, we analyzed the RNA sequencing of 90 patients with BCa. The results showed that the expression of SULF2 was closely related to the prognosis of BCa. Moreover, in vivo and in vitro experiments revealed that SULF2 promotes tumor proliferation and invasion. Furthermore, using a mouse orthotopic BCa model and flow cytometric analysis, we identified that SULF2 affects the polarization of macrophages. Mechanism studies clarified that SULF2 promoted the release of HSPG-binding factors, such as IL-8, in the microenvironment through β-catenin. Meanwhile, IL-8 activated the JAK2/STAT3 pathway of macrophages to promote the expression of CD163 and CD206, thereby regulating the polarization of macrophages to the M2-type. Conclusively, these results indicate that SULF2 plays an important role in regulating the microenvironment of BCa and promotes the polarization of macrophages to the M2-type by secreting IL-8, which further deepens the malignant progression of BCa. [ABSTRACT FROM AUTHOR]
- Subjects :
- INTERLEUKINS
STAT proteins
DISEASE progression
BLADDER tumors
IN vitro studies
BIOLOGICAL models
FLOW cytometry
REVERSE transcriptase polymerase chain reaction
IN vivo studies
SEQUENCE analysis
ANIMAL experimentation
WESTERN immunoblotting
COLONY-forming units assay
IMMUNOHISTOCHEMISTRY
LOG-rank test
ONE-way analysis of variance
MACROPHAGES
MANN Whitney U Test
CELLULAR signal transduction
JANUS kinases
CANCER patients
CELL proliferation
ENZYME-linked immunosorbent assay
DESCRIPTIVE statistics
SURVIVAL analysis (Biometry)
KAPLAN-Meier estimator
RESEARCH funding
TUMOR markers
NEUROTRANSMITTER uptake inhibitors
CELL lines
DATA analysis software
MICE
OVERALL survival
Subjects
Details
- Language :
- English
- ISSN :
- 20726694
- Volume :
- 15
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Cancers
- Publication Type :
- Academic Journal
- Accession number :
- 161189906
- Full Text :
- https://doi.org/10.3390/cancers15010131