Mast cells induce epithelial-to-mesenchymal transition and migration in non-small cell lung cancer through IL-8/Wnt/ß-catenin pathway.
J Cancer
; 10(16): 3830-3841, 2019.
Article
em En
| MEDLINE
| ID: mdl-31333800
ABSTRACT
Background:
In the various cancer, mast cells (MCs) infiltration is correlated with a worse prognosis. There is an increasing evidence that MCs and their mediators are participated in remodeling of the tumor microenvironment and facilitate tumor growth, epithelial-to-mesenchymal transition (EMT) and metastasis.Methods:
The transwell was conducted to evaluate the correlations between MCs and non-small cell lung cancer (NSCLC) cells in vitro. The RNA interference of ß-catenin was performed to further explore the signaling pathway. Lung adenocarcinoma cell line A549 and human MC (HMC-1) were subcutaneously injected into BALB/c nude mice. The conventional experiment methods (such as quantitative RT-PCR Western Blot, Immunofluorescence, and ELISA) were used in the present study.Results:
We found that high density of MCs in NSCLC correlates with worse prognosis. The NSCLC cells could release CCL5 and recruit MCs to the tumor microenvironment. Then, we explored that HMC-1 transplantation accelerated the growth of A549 cell in nude mice. Moreover, the MCs-derived factors were responsible for tumor growth. When NSCLC cells were activated, MCs produced various factors that induced EMT and migration. We also identified that CXCL8/interleukin (IL)-8 served as the major modulator containing in the activated MC conditioned medium. Furthermore, MCs and exogenous IL-8 promoted ß-catenin phosphorylation in NSCLC cells. Inhibiting the Wnt/ß-catenin pathway by RNA interference could revert EMT and migration of NSCLC.Conclusions:
Our study suggests that MCs are recruited into NSCLC microenvironment and improve the EMT and migration of cancer cells, thereby accelerating the growth of NSCLC.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article