Cargando…

Interleukin-22 Mediates the Chemotactic Migration of Breast Cancer Cells and Macrophage Infiltration of the Bone Microenvironment by Potentiating S1P/SIPR Signaling

The interleukin-22 (IL-22) signaling pathway is well known to be involved in the progression of various cancer types but its role in bone metastatic breast cancer remains unclear. We demonstrate using human GEO profiling that bone metastatic breast cancer displays elevated interleukin-22 receptor 1...

Descripción completa

Detalles Bibliográficos
Autores principales: Kim, Eun-Young, Choi, Bongkun, Kim, Ji-Eun, Park, Si-On, Kim, Sang-Min, Chang, Eun-Ju
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017200/
https://www.ncbi.nlm.nih.gov/pubmed/31935914
http://dx.doi.org/10.3390/cells9010131
_version_ 1783497148148482048
author Kim, Eun-Young
Choi, Bongkun
Kim, Ji-Eun
Park, Si-On
Kim, Sang-Min
Chang, Eun-Ju
author_facet Kim, Eun-Young
Choi, Bongkun
Kim, Ji-Eun
Park, Si-On
Kim, Sang-Min
Chang, Eun-Ju
author_sort Kim, Eun-Young
collection PubMed
description The interleukin-22 (IL-22) signaling pathway is well known to be involved in the progression of various cancer types but its role in bone metastatic breast cancer remains unclear. We demonstrate using human GEO profiling that bone metastatic breast cancer displays elevated interleukin-22 receptor 1 (IL-22R1) and sphingosine-1-phosphate receptor 1 (S1PR1) expression. Importantly, IL-22 stimuli promoted the expression of IL-22R1 and S1PR1 in aggressive MDA-MB-231 breast cancer cells. IL-22 treatment also increased sphingosine-1-phosphate production in mesenchymal stem cells (MSCs) and induced the sphingosine-1-phosphate (S1P)-mediated chemotactic migration of MDA-MB-231 cells. This effect was inhibited by an S1P antagonist. In addition to the S1PR1 axis, IL-22 stimulated the expression of matrix metalloproteinase-9 (MMP-9), thereby promoting breast cancer cell invasion. Moreover, IL-22 induced IL22R1 and S1PR1 expression in macrophages, myeloid cell, and MCP1 expression in MSCs to facilitate macrophage infiltration. Immunohistochemistry indicated that IL-22R1 and S1PR1 are overexpressed in invasive malignant breast cancers and that this correlates with the MMP-9 levels. Collectively, our present results indicate a potential role of IL-22 in driving the metastasis of breast cancers into the bone microenvironment through the IL22R1-S1PR1 axis.
format Online
Article
Text
id pubmed-7017200
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-70172002020-02-28 Interleukin-22 Mediates the Chemotactic Migration of Breast Cancer Cells and Macrophage Infiltration of the Bone Microenvironment by Potentiating S1P/SIPR Signaling Kim, Eun-Young Choi, Bongkun Kim, Ji-Eun Park, Si-On Kim, Sang-Min Chang, Eun-Ju Cells Article The interleukin-22 (IL-22) signaling pathway is well known to be involved in the progression of various cancer types but its role in bone metastatic breast cancer remains unclear. We demonstrate using human GEO profiling that bone metastatic breast cancer displays elevated interleukin-22 receptor 1 (IL-22R1) and sphingosine-1-phosphate receptor 1 (S1PR1) expression. Importantly, IL-22 stimuli promoted the expression of IL-22R1 and S1PR1 in aggressive MDA-MB-231 breast cancer cells. IL-22 treatment also increased sphingosine-1-phosphate production in mesenchymal stem cells (MSCs) and induced the sphingosine-1-phosphate (S1P)-mediated chemotactic migration of MDA-MB-231 cells. This effect was inhibited by an S1P antagonist. In addition to the S1PR1 axis, IL-22 stimulated the expression of matrix metalloproteinase-9 (MMP-9), thereby promoting breast cancer cell invasion. Moreover, IL-22 induced IL22R1 and S1PR1 expression in macrophages, myeloid cell, and MCP1 expression in MSCs to facilitate macrophage infiltration. Immunohistochemistry indicated that IL-22R1 and S1PR1 are overexpressed in invasive malignant breast cancers and that this correlates with the MMP-9 levels. Collectively, our present results indicate a potential role of IL-22 in driving the metastasis of breast cancers into the bone microenvironment through the IL22R1-S1PR1 axis. MDPI 2020-01-06 /pmc/articles/PMC7017200/ /pubmed/31935914 http://dx.doi.org/10.3390/cells9010131 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kim, Eun-Young
Choi, Bongkun
Kim, Ji-Eun
Park, Si-On
Kim, Sang-Min
Chang, Eun-Ju
Interleukin-22 Mediates the Chemotactic Migration of Breast Cancer Cells and Macrophage Infiltration of the Bone Microenvironment by Potentiating S1P/SIPR Signaling
title Interleukin-22 Mediates the Chemotactic Migration of Breast Cancer Cells and Macrophage Infiltration of the Bone Microenvironment by Potentiating S1P/SIPR Signaling
title_full Interleukin-22 Mediates the Chemotactic Migration of Breast Cancer Cells and Macrophage Infiltration of the Bone Microenvironment by Potentiating S1P/SIPR Signaling
title_fullStr Interleukin-22 Mediates the Chemotactic Migration of Breast Cancer Cells and Macrophage Infiltration of the Bone Microenvironment by Potentiating S1P/SIPR Signaling
title_full_unstemmed Interleukin-22 Mediates the Chemotactic Migration of Breast Cancer Cells and Macrophage Infiltration of the Bone Microenvironment by Potentiating S1P/SIPR Signaling
title_short Interleukin-22 Mediates the Chemotactic Migration of Breast Cancer Cells and Macrophage Infiltration of the Bone Microenvironment by Potentiating S1P/SIPR Signaling
title_sort interleukin-22 mediates the chemotactic migration of breast cancer cells and macrophage infiltration of the bone microenvironment by potentiating s1p/sipr signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017200/
https://www.ncbi.nlm.nih.gov/pubmed/31935914
http://dx.doi.org/10.3390/cells9010131
work_keys_str_mv AT kimeunyoung interleukin22mediatesthechemotacticmigrationofbreastcancercellsandmacrophageinfiltrationofthebonemicroenvironmentbypotentiatings1psiprsignaling
AT choibongkun interleukin22mediatesthechemotacticmigrationofbreastcancercellsandmacrophageinfiltrationofthebonemicroenvironmentbypotentiatings1psiprsignaling
AT kimjieun interleukin22mediatesthechemotacticmigrationofbreastcancercellsandmacrophageinfiltrationofthebonemicroenvironmentbypotentiatings1psiprsignaling
AT parksion interleukin22mediatesthechemotacticmigrationofbreastcancercellsandmacrophageinfiltrationofthebonemicroenvironmentbypotentiatings1psiprsignaling
AT kimsangmin interleukin22mediatesthechemotacticmigrationofbreastcancercellsandmacrophageinfiltrationofthebonemicroenvironmentbypotentiatings1psiprsignaling
AT changeunju interleukin22mediatesthechemotacticmigrationofbreastcancercellsandmacrophageinfiltrationofthebonemicroenvironmentbypotentiatings1psiprsignaling