Difference of TGF-ß/Smads signaling pathway in epithelial-mesenchymal transition of normal colonic epithelial cells induced by tumor-associated fibroblasts and colon cancer cells.
Mol Biol Rep
; 46(3): 2749-2759, 2019 Jun.
Article
em En
| MEDLINE
| ID: mdl-30835040
ABSTRACT
Tumor microenvironment (TME) crucially functions in tumor initiation and progression. Stroma-tumor interactions and cellular transdifferentiation are the prerequisite for tumor formation. Transforming growth factor-ß (TGF-ß), a major cytokine secreted by tumor-associated fibroblasts (TAFs) and cancer cells, is a crucial player involving cell transdifferentiation. Therefore, we hypothesized that these TAFs and cancer cells also affect normal colon epithelium. In our study, we found for the first time that colon cancer cells HCT116 and TAF-like CCD-18Co cells induced epithelial-mesenchymal transition (EMT)-like transdifferentiation in colon epithelial cells HCoEpiCs, with enhanced migratio. Dysfunction of TGF-ß/Smads signal was also observed in the EMT-transformed HCoEpiCs. We wondered whether these phenomena were regulated by TGF-ß/Smads signaling pathway. A TGFß receptor kinase I (TßRI) inhibitor LY364947 was used. We found that the EMT induced by the HCT116- and CCD-18Co-derived CM was suppressed by the LY364947. Besides, different expression profiles for the components of TGF-ß/Smads pathway were found in the EMT-like HCoEpiCs, but high expression of p-Smad2/3 and Smad4 was the common feature. Our observations suggest that the mechanisms of phenotypic transition of colon epithelial cells are cellular environment-dependent, which maybe a basis of potential therapy targeting TME.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias do Colo
/
Transdiferenciação Celular
/
Fibroblastos Associados a Câncer
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Mol Biol Rep
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China