Dissecting the autocrine and paracrine roles of the CCR2-CCL2 axis in tumor survival and angiogenesis.
The CCL2 CCR2 axis is likely to contributes to the development and progression of cancer diseases by two major mechanisms; autocrine effect of CCL2 as a survival/growth factor for CCR2+ cancer cells and, the attraction of CCR2+ CX₃CR1+tumor associated macrophages that in the absence of CCR2 hardly m...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3261135?pdf=render |
| _version_ | 1819019475867926528 |
|---|---|
| author | Liat Izhak Gizi Wildbaum Steffen Jung Avi Stein Yuval Shaked Nathan Karin |
| author_facet | Liat Izhak Gizi Wildbaum Steffen Jung Avi Stein Yuval Shaked Nathan Karin |
| author_sort | Liat Izhak |
| collection | DOAJ |
| description | The CCL2 CCR2 axis is likely to contributes to the development and progression of cancer diseases by two major mechanisms; autocrine effect of CCL2 as a survival/growth factor for CCR2+ cancer cells and, the attraction of CCR2+ CX₃CR1+tumor associated macrophages that in the absence of CCR2 hardly migrate. Thus far no in vivo system has been set up to differentiate the selective contribution of each of these features to cancer development. Here we employed a chimera animal model in which all non-malignant cells are CCR2-/-, but all cancer cells are CCR2+, combined with an adoptive transfer system of bone marrow (BM) CX₃CR1+ cells from CCR2+ mice harboring a targeted replacement of the CX₃CR1gene by an enhanced green fluorescent protein (EGFP) reporter gene (cx₃cr1(gfp)), together with the CD45.1 congene. Using this system we dissected the selective contribution of CX₃CR1+CCR2+ cells, which comprise only about 7% of CD11b+ BM cells, to tumor development and angiogenesis. Showing that aside for their direct pro-angiogenic effect they are essential for the recruitment of other CD11b+ cells to the tumor site. We further show that the administration of CCR2-Ig, that selectively and specifically neutralize CCL2, to mice in which CCR2 is expressed only on tumor cells, further suppressed tumor development, implicating for the key role of this chemokine supporting tumor survival in an autocrine manner. This further emphasizes the important role of CCL2 as a target for therapy of cancer diseases. |
| first_indexed | 2024-12-21T03:35:55Z |
| format | Article |
| id | doaj.art-49ce8331497440c2a34bbebb433f3857 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T03:35:55Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-49ce8331497440c2a34bbebb433f38572022-12-21T19:17:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0171e2830510.1371/journal.pone.0028305Dissecting the autocrine and paracrine roles of the CCR2-CCL2 axis in tumor survival and angiogenesis.Liat IzhakGizi WildbaumSteffen JungAvi SteinYuval ShakedNathan KarinThe CCL2 CCR2 axis is likely to contributes to the development and progression of cancer diseases by two major mechanisms; autocrine effect of CCL2 as a survival/growth factor for CCR2+ cancer cells and, the attraction of CCR2+ CX₃CR1+tumor associated macrophages that in the absence of CCR2 hardly migrate. Thus far no in vivo system has been set up to differentiate the selective contribution of each of these features to cancer development. Here we employed a chimera animal model in which all non-malignant cells are CCR2-/-, but all cancer cells are CCR2+, combined with an adoptive transfer system of bone marrow (BM) CX₃CR1+ cells from CCR2+ mice harboring a targeted replacement of the CX₃CR1gene by an enhanced green fluorescent protein (EGFP) reporter gene (cx₃cr1(gfp)), together with the CD45.1 congene. Using this system we dissected the selective contribution of CX₃CR1+CCR2+ cells, which comprise only about 7% of CD11b+ BM cells, to tumor development and angiogenesis. Showing that aside for their direct pro-angiogenic effect they are essential for the recruitment of other CD11b+ cells to the tumor site. We further show that the administration of CCR2-Ig, that selectively and specifically neutralize CCL2, to mice in which CCR2 is expressed only on tumor cells, further suppressed tumor development, implicating for the key role of this chemokine supporting tumor survival in an autocrine manner. This further emphasizes the important role of CCL2 as a target for therapy of cancer diseases.http://europepmc.org/articles/PMC3261135?pdf=render |
| spellingShingle | Liat Izhak Gizi Wildbaum Steffen Jung Avi Stein Yuval Shaked Nathan Karin Dissecting the autocrine and paracrine roles of the CCR2-CCL2 axis in tumor survival and angiogenesis. PLoS ONE |
| title | Dissecting the autocrine and paracrine roles of the CCR2-CCL2 axis in tumor survival and angiogenesis. |
| title_full | Dissecting the autocrine and paracrine roles of the CCR2-CCL2 axis in tumor survival and angiogenesis. |
| title_fullStr | Dissecting the autocrine and paracrine roles of the CCR2-CCL2 axis in tumor survival and angiogenesis. |
| title_full_unstemmed | Dissecting the autocrine and paracrine roles of the CCR2-CCL2 axis in tumor survival and angiogenesis. |
| title_short | Dissecting the autocrine and paracrine roles of the CCR2-CCL2 axis in tumor survival and angiogenesis. |
| title_sort | dissecting the autocrine and paracrine roles of the ccr2 ccl2 axis in tumor survival and angiogenesis |
| url | http://europepmc.org/articles/PMC3261135?pdf=render |
| work_keys_str_mv | AT liatizhak dissectingtheautocrineandparacrinerolesoftheccr2ccl2axisintumorsurvivalandangiogenesis AT giziwildbaum dissectingtheautocrineandparacrinerolesoftheccr2ccl2axisintumorsurvivalandangiogenesis AT steffenjung dissectingtheautocrineandparacrinerolesoftheccr2ccl2axisintumorsurvivalandangiogenesis AT avistein dissectingtheautocrineandparacrinerolesoftheccr2ccl2axisintumorsurvivalandangiogenesis AT yuvalshaked dissectingtheautocrineandparacrinerolesoftheccr2ccl2axisintumorsurvivalandangiogenesis AT nathankarin dissectingtheautocrineandparacrinerolesoftheccr2ccl2axisintumorsurvivalandangiogenesis |