Cargando…

Interleukin-8 released by cancer-associated fibroblasts attenuates the autophagy and promotes the migration of ovarian cancer cells

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Thongchot, Suyanee, Jamjuntra, Pranisa, Therasakvichya, Suwanit, Warnnissorn, Malee, Ferraresi, Alessandra, Thuwajit, Peti, Isidoro, Ciro, Thuwajit, Chanitra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7949624/
https://www.ncbi.nlm.nih.gov/pubmed/33649784
http://dx.doi.org/10.3892/ijo.2021.5194
_version_ 1783663520309575680
author Thongchot, Suyanee
Jamjuntra, Pranisa
Therasakvichya, Suwanit
Warnnissorn, Malee
Ferraresi, Alessandra
Thuwajit, Peti
Isidoro, Ciro
Thuwajit, Chanitra
author_facet Thongchot, Suyanee
Jamjuntra, Pranisa
Therasakvichya, Suwanit
Warnnissorn, Malee
Ferraresi, Alessandra
Thuwajit, Peti
Isidoro, Ciro
Thuwajit, Chanitra
author_sort Thongchot, Suyanee
collection PubMed
description 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 cancer-associated fibroblasts (OVCAFs) with their secretory substances on the autophagy and migration of ovarian cancer cells. The conditioned-medium (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 OVCAF-CM. The role of IL-8 in ovarian cancer cell migration and its mechanistic link with autophagy was investigated. Recombinant human IL-8 (rhIL-8) stimulated the migration of SKOV3 and Kuramochi ovarian cancer cells, and concurrently downregulated basal autophagy, in concentration-dependent manner. Compared to the CM of control counterpart normal fibroblasts isolated from benign ovaries (OVNF-CM), the CM from 3 OVCAF isolates (namely, OVCAF-9, -20 and -43) exerted effects similar to rhIL-8 on both cancer cell lines. The pharmacological induction of autophagy with rapamycin or metformin attenuated the pro-migratory effects of IL-8. Neutralizing anti-IL-8 antibody counteracted the inhibitory effect of OVCAF-CM on basal autophagy. On the whole, the present study highlights the involvement of IL-8 released by CAFs in the ovarian tumor microenvironment in promoting cancer cell migration through the suppression of autophagy.
format Online
Article
Text
id pubmed-7949624
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-79496242021-03-22 Interleukin-8 released by cancer-associated fibroblasts attenuates the autophagy and promotes the migration of ovarian cancer cells Thongchot, Suyanee Jamjuntra, Pranisa Therasakvichya, Suwanit Warnnissorn, Malee Ferraresi, Alessandra Thuwajit, Peti Isidoro, Ciro Thuwajit, Chanitra Int J Oncol Articles 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 cancer-associated fibroblasts (OVCAFs) with their secretory substances on the autophagy and migration of ovarian cancer cells. The conditioned-medium (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 OVCAF-CM. The role of IL-8 in ovarian cancer cell migration and its mechanistic link with autophagy was investigated. Recombinant human IL-8 (rhIL-8) stimulated the migration of SKOV3 and Kuramochi ovarian cancer cells, and concurrently downregulated basal autophagy, in concentration-dependent manner. Compared to the CM of control counterpart normal fibroblasts isolated from benign ovaries (OVNF-CM), the CM from 3 OVCAF isolates (namely, OVCAF-9, -20 and -43) exerted effects similar to rhIL-8 on both cancer cell lines. The pharmacological induction of autophagy with rapamycin or metformin attenuated the pro-migratory effects of IL-8. Neutralizing anti-IL-8 antibody counteracted the inhibitory effect of OVCAF-CM on basal autophagy. On the whole, the present study highlights the involvement of IL-8 released by CAFs in the ovarian tumor microenvironment in promoting cancer cell migration through the suppression of autophagy. D.A. Spandidos 2021-03-01 /pmc/articles/PMC7949624/ /pubmed/33649784 http://dx.doi.org/10.3892/ijo.2021.5194 Text en Copyright: © Thongchot et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Thongchot, Suyanee
Jamjuntra, Pranisa
Therasakvichya, Suwanit
Warnnissorn, Malee
Ferraresi, Alessandra
Thuwajit, Peti
Isidoro, Ciro
Thuwajit, Chanitra
Interleukin-8 released by cancer-associated fibroblasts attenuates the autophagy and promotes the migration of ovarian cancer cells
title Interleukin-8 released by cancer-associated fibroblasts attenuates the autophagy and promotes the migration of ovarian cancer cells
title_full Interleukin-8 released by cancer-associated fibroblasts attenuates the autophagy and promotes the migration of ovarian cancer cells
title_fullStr Interleukin-8 released by cancer-associated fibroblasts attenuates the autophagy and promotes the migration of ovarian cancer cells
title_full_unstemmed Interleukin-8 released by cancer-associated fibroblasts attenuates the autophagy and promotes the migration of ovarian cancer cells
title_short Interleukin-8 released by cancer-associated fibroblasts attenuates the autophagy and promotes the migration of ovarian cancer cells
title_sort interleukin-8 released by cancer-associated fibroblasts attenuates the autophagy and promotes the migration of ovarian cancer cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7949624/
https://www.ncbi.nlm.nih.gov/pubmed/33649784
http://dx.doi.org/10.3892/ijo.2021.5194
work_keys_str_mv AT thongchotsuyanee interleukin8releasedbycancerassociatedfibroblastsattenuatestheautophagyandpromotesthemigrationofovariancancercells
AT jamjuntrapranisa interleukin8releasedbycancerassociatedfibroblastsattenuatestheautophagyandpromotesthemigrationofovariancancercells
AT therasakvichyasuwanit interleukin8releasedbycancerassociatedfibroblastsattenuatestheautophagyandpromotesthemigrationofovariancancercells
AT warnnissornmalee interleukin8releasedbycancerassociatedfibroblastsattenuatestheautophagyandpromotesthemigrationofovariancancercells
AT ferraresialessandra interleukin8releasedbycancerassociatedfibroblastsattenuatestheautophagyandpromotesthemigrationofovariancancercells
AT thuwajitpeti interleukin8releasedbycancerassociatedfibroblastsattenuatestheautophagyandpromotesthemigrationofovariancancercells
AT isidorociro interleukin8releasedbycancerassociatedfibroblastsattenuatestheautophagyandpromotesthemigrationofovariancancercells
AT thuwajitchanitra interleukin8releasedbycancerassociatedfibroblastsattenuatestheautophagyandpromotesthemigrationofovariancancercells