Interleukin8 released by cancerassociated fibroblasts attenuates the autophagy and promotes the migration of ovarian cancer cells.
Int J Oncol
; 58(5)2021 05.
Article
en En
| MEDLINE
| ID: mdl-33649784
ABSTRACT
The tumor microenvironment composed of a mixture of stromal cells and their secretions has a marked impact on cancer progression. In particular, soluble factors and metabolites contribute to malignancy through the dysregulation of autophagy in cancer cells. The present study investigated the effects of ovarian cancerassociated fibroblasts (OVCAFs) with their secretory substances on the autophagy and migration of ovarian cancer cells. The conditionedmedium (CM) of OVCAFs isolated from fresh human ovarian cancer tissues was analyzed for the levels of 27 common cytokines/chemokines using a cytokine array. Autophagy in cancer cells was assessed by determining the expression of the vacuolar form of LC3 by western blot analysis and immunofluorescence. Cancer cell migration was assessed by Transwell migration assay. Interleukin (IL)8 was found to be the most highly upregulated cytokine among the cytokines/chemokines found in the OVCAFCM. The role of IL8 in ovarian cancer cell migration and its mechanistic link with autophagy was investigated. Recombinant human IL8 (rhIL8) stimulated the migration of SKOV3 and Kuramochi ovarian cancer cells, and concurrently downregulated basal autophagy, in concentrationdependent manner. Compared to the CM of control counterpart normal fibroblasts isolated from benign ovaries (OVNFCM), the CM from 3 OVCAF isolates (namely, OVCAF9, 20 and 43) exerted effects similar to rhIL8 on both cancer cell lines. The pharmacological induction of autophagy with rapamycin or metformin attenuated the promigratory effects of IL8. Neutralizing antiIL8 antibody counteracted the inhibitory effect of OVCAFCM on basal autophagy. On the whole, the present study highlights the involvement of IL8 released by CAFs in the ovarian tumor microenvironment in promoting cancer cell migration through the suppression of autophagy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
/
Regulación hacia Arriba
/
Interleucina-8
/
Fibroblastos Asociados al Cáncer
Tipo de estudio:
Risk_factors_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Int J Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2021
Tipo del documento:
Article
País de afiliación:
Tailandia