Pancreatic cancer cell-derived exosomes induce epithelial-mesenchymal transition in human pancreatic cancer cells themselves partially via transforming growth factor ß1.
Med Mol Morphol
; 55(3): 227-235, 2022 Sep.
Article
en En
| MEDLINE
| ID: mdl-35475918
ABSTRACT
Distant metastasis is a dismal prognostic factor of pancreatic cancer. Metastasis is established in several steps, but the mechanism underlying the very early stages remains unclear. Epithelial-mesenchymal transition (EMT) is involved in these stages. Although signaling molecules have been reported to induce EMT, the mechanism underlying their origin is unclear. In this study, we hypothesized that pancreatic cancer cell-derived exosomes induce EMT in cancer cells themselves, a notion we entertained because we found EMT in in vitro three-dimensional colonies of cancer cells, with vimentin-positive cells observed in some of the budding pancreatic cancer cells and in single cells outside the colony as well. First, we clarified that pancreatic cancer cell-derived exosomes induce EMT in cancer cells themselves. Next, we examined the involvement of transforming growth factor-ß1 (TGF-ß1), and TGF-ß1 knock-down in pancreatic cancer cells with TGF-ß1 siRNA significantly suppressed TGF-ß1 gene expression in cancer cells, and exosomal TGF-ß1 was significantly reduced in the secretory exosomes. Exosomes from TGF-ß1 knock-down cells suppressed EMT induction in cancer cells themselves and TGF-ß1 protein expression in target cells. Taken together, these findings suggest that TGF-ß1 is involved in EMT induction via exosomes, results that may support the production of effective metastasis inhibitors.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Pancreáticas
/
Factor de Crecimiento Transformador beta1
/
Exosomas
/
Transición Epitelial-Mesenquimal
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Med Mol Morphol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
PATOLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Japón