Crosstalk of renal cell carcinoma cells and tumor-associated macrophages aggravates tumor progression by modulating muscleblind-like protein 2/B-cell lymphoma 2/beclin 1-mediated autophagy.
Cytotherapy
; 25(3): 298-309, 2023 03.
Article
em En
| MEDLINE
| ID: mdl-36244911
ABSTRACT
BACKGROUND AIMS:
M2-polarized tumor-associated macrophages contribute to the development of multiple human cancers, including renal cell carcinoma (RCC). However, the crosstalk mechanism between M2 macrophages and RCC remains unclear.METHODS:
The authors constructed a co-culture system of M2 macrophages differentiated from THP-1 and RCC cells. Microscopic examination and quantitative realtime polymerase chain reaction (qRT-PCR) validated the morphology and types of macrophages. The proliferation, migration and invasion of RCC cells were assessed by Cell Counting Kit 8 (Dojindo Molecular Technologies, Inc, Santa Clara, CA, USA) and Transwell assay (Corning, Corning, NY, USA). Messenger RNA (mRNA) and protein expression of target molecules was detected by qRTPCR and western blotting. Expression of Ki-67, E-cadherin and N-cadherin was measured by immunofluorescence staining or immunohistochemistry. Molecular interaction was evaluated by RNA pull-down, RNA immunoprecipitation and co-immunoprecipitation. A xenograft model was established to determine tumor growth in vivo.RESULTS:
RCC cells triggered the activation of M2 macrophages. Functionally, M2-polarized macrophages facilitated the growth, migration, invasion and epithelial-mesenchymal transition of RCC cells by suppressing autophagy, whereas rapamycin, an activator of autophagy, significantly counteracted the tumor-promoting effects of M2 macrophages. Mechanistically, M2 macrophage-derived C-C motif chemokine 2 (CCL2) enhanced modulation of muscleblind-like protein 2 (MBNL2) expression. MBNL2 raised the stability of B-cell lymphoma 2 (Bcl-2) by directly binding to Bcl-2 mRNA, which endowed RCC cells with malignant properties via inhibition of beclin 1-dependent autophagy.CONCLUSIONS:
RCC-induced M2-polarized macrophages secrete CCL2 to promote the growth and metastasis of RCC cells via inhibition of MBNL2/Bcl-2/beclin 1-mediated autophagy, which provide a novel perspective for the development of a therapeutic strategy for -RCC.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Carcinoma de Células Renais
/
Neoplasias Renais
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article