Mesenchymal transition and dissemination of cancer cells is driven by myeloid-derived suppressor cells infiltrating the primary tumor.
In order to metastasize, cancer cells need to acquire a motile phenotype. Previously, development of this phenotype was thought to rely on the acquisition of selected, random mutations and thus would occur late in cancer progression. However, recent studies show that cancer cells disseminate early,...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-09-01
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| Series: | PLoS Biology |
| Online Access: | http://europepmc.org/articles/PMC3181226?pdf=render |
| _version_ | 1818623111391608832 |
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| author | Benjamin Toh Xiaojie Wang Jo Keeble Wen Jing Sim Karen Khoo Wing-Cheong Wong Masashi Kato Armelle Prevost-Blondel Jean-Paul Thiery Jean-Pierre Abastado |
| author_facet | Benjamin Toh Xiaojie Wang Jo Keeble Wen Jing Sim Karen Khoo Wing-Cheong Wong Masashi Kato Armelle Prevost-Blondel Jean-Paul Thiery Jean-Pierre Abastado |
| author_sort | Benjamin Toh |
| collection | DOAJ |
| description | In order to metastasize, cancer cells need to acquire a motile phenotype. Previously, development of this phenotype was thought to rely on the acquisition of selected, random mutations and thus would occur late in cancer progression. However, recent studies show that cancer cells disseminate early, implying the existence of a different, faster route to the metastatic motile phenotype. Using a spontaneous murine model of melanoma, we show that a subset of bone marrow-derived immune cells (myeloid-derived suppressor cells or MDSC) preferentially infiltrates the primary tumor and actively promotes cancer cell dissemination by inducing epithelial-mesenchymal transition (EMT). CXCL5 is the main chemokine attracting MDSC to the primary tumor. In vitro assay using purified MDSC showed that TGF-β, EGF, and HGF signaling pathways are all used by MDSC to induce EMT in cancer cells. These findings explain how cancer cells acquire a motile phenotype so early and provide a mechanistic explanation for the long recognized link between inflammation and cancer progression. |
| first_indexed | 2024-12-16T18:35:52Z |
| format | Article |
| id | doaj.art-f44fa3332e3745aa89fe92e74ac7d26f |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-16T18:35:52Z |
| publishDate | 2011-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-f44fa3332e3745aa89fe92e74ac7d26f2022-12-21T22:21:10ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852011-09-0199e100116210.1371/journal.pbio.1001162Mesenchymal transition and dissemination of cancer cells is driven by myeloid-derived suppressor cells infiltrating the primary tumor.Benjamin TohXiaojie WangJo KeebleWen Jing SimKaren KhooWing-Cheong WongMasashi KatoArmelle Prevost-BlondelJean-Paul ThieryJean-Pierre AbastadoIn order to metastasize, cancer cells need to acquire a motile phenotype. Previously, development of this phenotype was thought to rely on the acquisition of selected, random mutations and thus would occur late in cancer progression. However, recent studies show that cancer cells disseminate early, implying the existence of a different, faster route to the metastatic motile phenotype. Using a spontaneous murine model of melanoma, we show that a subset of bone marrow-derived immune cells (myeloid-derived suppressor cells or MDSC) preferentially infiltrates the primary tumor and actively promotes cancer cell dissemination by inducing epithelial-mesenchymal transition (EMT). CXCL5 is the main chemokine attracting MDSC to the primary tumor. In vitro assay using purified MDSC showed that TGF-β, EGF, and HGF signaling pathways are all used by MDSC to induce EMT in cancer cells. These findings explain how cancer cells acquire a motile phenotype so early and provide a mechanistic explanation for the long recognized link between inflammation and cancer progression.http://europepmc.org/articles/PMC3181226?pdf=render |
| spellingShingle | Benjamin Toh Xiaojie Wang Jo Keeble Wen Jing Sim Karen Khoo Wing-Cheong Wong Masashi Kato Armelle Prevost-Blondel Jean-Paul Thiery Jean-Pierre Abastado Mesenchymal transition and dissemination of cancer cells is driven by myeloid-derived suppressor cells infiltrating the primary tumor. PLoS Biology |
| title | Mesenchymal transition and dissemination of cancer cells is driven by myeloid-derived suppressor cells infiltrating the primary tumor. |
| title_full | Mesenchymal transition and dissemination of cancer cells is driven by myeloid-derived suppressor cells infiltrating the primary tumor. |
| title_fullStr | Mesenchymal transition and dissemination of cancer cells is driven by myeloid-derived suppressor cells infiltrating the primary tumor. |
| title_full_unstemmed | Mesenchymal transition and dissemination of cancer cells is driven by myeloid-derived suppressor cells infiltrating the primary tumor. |
| title_short | Mesenchymal transition and dissemination of cancer cells is driven by myeloid-derived suppressor cells infiltrating the primary tumor. |
| title_sort | mesenchymal transition and dissemination of cancer cells is driven by myeloid derived suppressor cells infiltrating the primary tumor |
| url | http://europepmc.org/articles/PMC3181226?pdf=render |
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