Article: Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells
| Title | Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells | ||||||||||||||
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| Authors | Yang, M1 3 Chen, J3 Su, F3 Yu, B1 Su, F3 Lin, L2 3 Liu, Y3 Huang, JD1 Song, E3 | ||||||||||||||
| Issue Date | 2011 | ||||||||||||||
| Publisher | BioMed 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?] DOI: http://dx.doi.org/10.1186/1476-4598-10-117 | ||||||||||||||
| 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. | ||||||||||||||
| ISSN | 1476-4598 2011 Impact Factor: 3.993 2011 SCImago Journal Rankings: 0.504 | ||||||||||||||
| DOI | http://dx.doi.org/10.1186/1476-4598-10-117 | ||||||||||||||
| ISI Accession Number ID | WOS:000295831200002
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). | ||||||||||||||
| PubMed Central ID | PMC3190352 21939504 | ||||||||||||||
| References | References in Scopus | ||||||||||||||
| Grants | Programming the Second Generation Tumor-targeting Bacteria |
| dc.contributor.author | Yang, M | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| dc.contributor.author | Chen, J | ||||||||||||||
| dc.contributor.author | Su, F | ||||||||||||||
| dc.contributor.author | Yu, B | ||||||||||||||
| dc.contributor.author | Su, F | ||||||||||||||
| dc.contributor.author | Lin, L | ||||||||||||||
| dc.contributor.author | Liu, Y | ||||||||||||||
| dc.contributor.author | Huang, JD | ||||||||||||||
| dc.contributor.author | Song, E | ||||||||||||||
| dc.date.accessioned | 2012-05-29T06:05:09Z | ||||||||||||||
| dc.date.available | 2012-05-29T06:05:09Z | ||||||||||||||
| dc.date.issued | 2011 | ||||||||||||||
| dc.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-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.grant | Programming the Second Generation Tumor-targeting Bacteria | ||||||||||||||
| dc.description.grantcode | 103836 | ||||||||||||||
| dc.description.nature | published_or_final_version | ||||||||||||||
| dc.identifier.citation | Molecular Cancer, 2011, v. 10, article no. 117 [How to Cite?] DOI: http://dx.doi.org/10.1186/1476-4598-10-117 | ||||||||||||||
| dc.identifier.citeulike | 9811212 | ||||||||||||||
| dc.identifier.doi | http://dx.doi.org/10.1186/1476-4598-10-117 | ||||||||||||||
| dc.identifier.hkuros | 208900 | ||||||||||||||
| dc.identifier.isi | WOS:000295831200002
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.issn | 1476-4598 2011 Impact Factor: 3.993 2011 SCImago Journal Rankings: 0.504 | ||||||||||||||
| dc.identifier.pmcid | PMC3190352 | ||||||||||||||
| dc.identifier.pmcid | 21939504 | ||||||||||||||
| dc.identifier.scopus | eid_2-s2.0-80053175966 | ||||||||||||||
| dc.identifier.uri | http://hdl.handle.net/10722/147639 | ||||||||||||||
| dc.identifier.volume | 10 | ||||||||||||||
| dc.language | eng | ||||||||||||||
| dc.publisher | BioMed Central Ltd. The Journal's web site is located at http://www.molecular-cancer.com | ||||||||||||||
| dc.publisher.place | United Kingdom | ||||||||||||||
| dc.relation.ispartof | Molecular Cancer | ||||||||||||||
| dc.relation.references | References in Scopus | ||||||||||||||
| dc.rights | Creative Commons: Attribution 3.0 Hong Kong License | ||||||||||||||
| dc.subject.mesh | Breast Neoplasms - metabolism - pathology - secretion | ||||||||||||||
| dc.subject.mesh | Exosomes - metabolism - secretion | ||||||||||||||
| dc.subject.mesh | MADS Domain Proteins - genetics - metabolism | ||||||||||||||
| dc.subject.mesh | Macrophages - drug effects - metabolism - secretion | ||||||||||||||
| dc.subject.mesh | MicroRNAs - genetics - metabolism - secretion | ||||||||||||||
| dc.title | Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells | ||||||||||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong
- Shantou University, Medical College (SUMC)
- Sun Yat-Sen University