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Article: Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells
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TitleMicrovesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells
 
AuthorsYang, M3 1
Chen, J3
Su, F3
Yu, B1
Su, F3
Lin, L3 2
Liu, Y3
Huang, JD1
Song, E3
 
Issue Date2011
 
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.molecular-cancer.com
 
CitationMolecular Cancer, 2011, v. 10, article no. 117 [How to Cite?]
DOI: http://dx.doi.org/10.1186/1476-4598-10-117
 
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.
 
ISSN1476-4598
2012 Impact Factor: 5.134
2012 SCImago Journal Rankings: 2.065
 
DOIhttp://dx.doi.org/10.1186/1476-4598-10-117
 
PubMed Central IDPMC3190352
21939504
 
ISI Accession Number IDWOS:000295831200002
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).

 
ReferencesReferences in Scopus
 
GrantsProgramming the Second Generation Tumor-targeting Bacteria
 
DC FieldValue
dc.contributor.authorYang, M
 
dc.contributor.authorChen, J
 
dc.contributor.authorSu, F
 
dc.contributor.authorYu, B
 
dc.contributor.authorSu, F
 
dc.contributor.authorLin, L
 
dc.contributor.authorLiu, Y
 
dc.contributor.authorHuang, JD
 
dc.contributor.authorSong, E
 
dc.date.accessioned2012-05-29T06:05:09Z
 
dc.date.available2012-05-29T06:05:09Z
 
dc.date.issued2011
 
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.
 
dc.description.naturepublished_or_final_version
 
dc.identifier.citationMolecular Cancer, 2011, v. 10, article no. 117 [How to Cite?]
DOI: http://dx.doi.org/10.1186/1476-4598-10-117
 
dc.identifier.citeulike9811212
 
dc.identifier.doihttp://dx.doi.org/10.1186/1476-4598-10-117
 
dc.identifier.hkuros208900
 
dc.identifier.isiWOS:000295831200002
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).

 
dc.identifier.issn1476-4598
2012 Impact Factor: 5.134
2012 SCImago Journal Rankings: 2.065
 
dc.identifier.pmcidPMC3190352
 
dc.identifier.pmcid21939504
 
dc.identifier.scopuseid_2-s2.0-80053175966
 
dc.identifier.urihttp://hdl.handle.net/10722/147639
 
dc.identifier.volume10
 
dc.languageeng
 
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.molecular-cancer.com
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofMolecular Cancer
 
dc.relation.projectProgramming the Second Generation Tumor-targeting Bacteria
 
dc.relation.referencesReferences in Scopus
 
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 cells
 
dc.typeArticle
 
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<contributor.author>Yu, B</contributor.author>
<contributor.author>Su, F</contributor.author>
<contributor.author>Lin, L</contributor.author>
<contributor.author>Liu, Y</contributor.author>
<contributor.author>Huang, JD</contributor.author>
<contributor.author>Song, E</contributor.author>
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<description.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-&#946;-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. &#169; 2011 Yang et al; licensee BioMed Central Ltd.</description.abstract>
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Author Affiliations
  1. The University of Hong Kong
  2. Shantou University, Medical College (SUMC)
  3. Sun Yat-Sen University