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Article: Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells

TitleMicrovesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells
Authors
Issue Date2011
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.molecular-cancer.com
Citation
Molecular Cancer, 2011, v. 10, article no. 117 How to Cite?
Abstract
Background: Tumor-associated macrophages (TAMs) are alternatively activated cells induced by interleukin-4 (IL-4)-releasing CD4 + T cells. TAMs promote breast cancer invasion and metastasis; however, the mechanisms underlying these interactions between macrophages and tumor cells that lead to cancer metastasis remain elusive. Previous studies have found microRNAs (miRNAs) circulating in the peripheral blood and have identified microvesicles, or exosomes, as mediators of cell-cell communication. Therefore, one alternative mechanism for the promotion of breast cancer cell invasion by TAMs may be through macrophage-secreted exosomes, which would deliver invasion-potentiating miRNAs to breast cancer cells.Results: We utilized a co-culture system with IL-4-activated macrophages and breast cancer cells to verify that miRNAs are transported from macrophages to breast cancer cells. The shuttling of fluorescently-labeled exogenous miRNAs from IL-4-activated macrophages to co-cultivated breast cancer cells without direct cell-cell contact was observed. miR-223, a miRNA specific for IL-4-activated macrophages, was detected within the exosomes released by macrophages and was significantly elevated in the co-cultivated SKBR3 and MDA-MB-231 cells. The invasiveness of the co-cultivated breast cancer cells decreased when the IL-4-activated macrophages were treated with a miR-223 antisense oligonucleotide (ASO) that would inhibit miR-223 expression. Furthermore, results from a functional assay revealed that miR-223 promoted the invasion of breast cancer cells via the Mef2c-β-catenin pathway.Conclusions: We conclude that macrophages regulate the invasiveness of breast cancer cells through exosome-mediated delivery of oncogenic miRNAs. Our data provide insight into the mechanisms underlying the metastasis-promoting interactions between macrophages and breast cancer cells. © 2011 Yang et al; licensee BioMed Central Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/147639
ISSN
2013 Impact Factor: 5.397
2013 SCImago Journal Rankings: 2.876
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
National Natural Science Foundation of ChinaNSFC30972785
30921140312
30831160515
30830110
Research Grants Council of Hong KongN_ HKU 719/08
HKU1/CRF/10
Ministry of Science and Technology of China2010CB912800
2011CB504203
2009CB521706
Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-Sen UniversityKLB09001
Public Health Administration of China
Ministry of Health of China2011ZX09102-010-02
Funding Information:

This work was supported by grants from the National Natural Science Foundation of China (NSFC30972785, 30921140312, 30831160515, and 30830110), the Research Grants Council of Hong Kong (N_ HKU 719/08 and HKU1/CRF/10) to ES and JDH, "973" Program Projects (2010CB912800, 2011CB504203, and 2009CB521706) from the Ministry of Science and Technology of China to ES, the Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-Sen University (KLB09001) to ES, the Clinical Key Project of Public Health Administration of China, and the Grant for Development of Important New Drugs from Ministry of Health of China (2011ZX09102-010-02).

References
Grants

 

Author Affiliations
  1. The University of Hong Kong
  2. Shantou University, Medical College (SUMC)
  3. Sun Yat-Sen University
DC FieldValueLanguage
dc.contributor.authorYang, Men_US
dc.contributor.authorChen, Jen_US
dc.contributor.authorSu, Fen_US
dc.contributor.authorYu, Ben_US
dc.contributor.authorSu, Fen_US
dc.contributor.authorLin, Len_US
dc.contributor.authorLiu, Yen_US
dc.contributor.authorHuang, JDen_US
dc.contributor.authorSong, Een_US
dc.date.accessioned2012-05-29T06:05:09Z-
dc.date.available2012-05-29T06:05:09Z-
dc.date.issued2011en_US
dc.identifier.citationMolecular Cancer, 2011, v. 10, article no. 117en_US
dc.identifier.issn1476-4598en_US
dc.identifier.urihttp://hdl.handle.net/10722/147639-
dc.description.abstractBackground: Tumor-associated macrophages (TAMs) are alternatively activated cells induced by interleukin-4 (IL-4)-releasing CD4 + T cells. TAMs promote breast cancer invasion and metastasis; however, the mechanisms underlying these interactions between macrophages and tumor cells that lead to cancer metastasis remain elusive. Previous studies have found microRNAs (miRNAs) circulating in the peripheral blood and have identified microvesicles, or exosomes, as mediators of cell-cell communication. Therefore, one alternative mechanism for the promotion of breast cancer cell invasion by TAMs may be through macrophage-secreted exosomes, which would deliver invasion-potentiating miRNAs to breast cancer cells.Results: We utilized a co-culture system with IL-4-activated macrophages and breast cancer cells to verify that miRNAs are transported from macrophages to breast cancer cells. The shuttling of fluorescently-labeled exogenous miRNAs from IL-4-activated macrophages to co-cultivated breast cancer cells without direct cell-cell contact was observed. miR-223, a miRNA specific for IL-4-activated macrophages, was detected within the exosomes released by macrophages and was significantly elevated in the co-cultivated SKBR3 and MDA-MB-231 cells. The invasiveness of the co-cultivated breast cancer cells decreased when the IL-4-activated macrophages were treated with a miR-223 antisense oligonucleotide (ASO) that would inhibit miR-223 expression. Furthermore, results from a functional assay revealed that miR-223 promoted the invasion of breast cancer cells via the Mef2c-β-catenin pathway.Conclusions: We conclude that macrophages regulate the invasiveness of breast cancer cells through exosome-mediated delivery of oncogenic miRNAs. Our data provide insight into the mechanisms underlying the metastasis-promoting interactions between macrophages and breast cancer cells. © 2011 Yang et al; licensee BioMed Central Ltd.en_US
dc.languageengen_US
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.molecular-cancer.comen_US
dc.relation.ispartofMolecular Canceren_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshBreast Neoplasms - metabolism - pathology - secretion-
dc.subject.meshExosomes - metabolism - secretion-
dc.subject.meshMADS Domain Proteins - genetics - metabolism-
dc.subject.meshMacrophages - drug effects - metabolism - secretion-
dc.subject.meshMicroRNAs - genetics - metabolism - secretion-
dc.titleMicrovesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cellsen_US
dc.typeArticleen_US
dc.identifier.emailHuang, JD:jdhuang@hkucc.hku.hken_US
dc.identifier.authorityHuang, JD=rp00451en_US
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1186/1476-4598-10-117en_US
dc.identifier.pmcidPMC3190352-
dc.identifier.pmcidPMC21939504-
dc.identifier.scopuseid_2-s2.0-80053175966en_US
dc.identifier.hkuros208900-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80053175966&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume10en_US
dc.identifier.isiWOS:000295831200002-
dc.publisher.placeUnited Kingdomen_US
dc.relation.projectProgramming the Second Generation Tumor-targeting Bacteria-
dc.identifier.scopusauthoridYang, M=52664493500en_US
dc.identifier.scopusauthoridChen, J=37086988100en_US
dc.identifier.scopusauthoridSu, F=7102864885en_US
dc.identifier.scopusauthoridYu, B=50263644200en_US
dc.identifier.scopusauthoridSu, F=41762753900en_US
dc.identifier.scopusauthoridLin, L=48061109000en_US
dc.identifier.scopusauthoridLiu, Y=52663693900en_US
dc.identifier.scopusauthoridHuang, JD=8108660600en_US
dc.identifier.scopusauthoridSong, E=7101904256en_US
dc.identifier.citeulike9811212-

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