Journal article
Dissecting the Autocrine and Paracrine Roles of the CCR2-CCL2 Axis in Tumor Survival and Angiogenesis
PLoS ONE, Vol.7(1)
Jan/2012
Abstract
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+ CX(3)CR1+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) CX(3)CR1+ cells from CCR2+ mice harboring a targeted replacement of the CX(3)CR1gene by an enhanced green fluorescent protein (EGFP) reporter gene (cx(3)cr1(gfp)), together with the CD45.1 congene. Using this system we dissected the selective contribution of CX(3)CR1+ 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.
Details
- Title
- Dissecting the Autocrine and Paracrine Roles of the CCR2-CCL2 Axis in Tumor Survival and Angiogenesis
- Creators
- Liat Izhak (null)Gizi Wildbaum (null)Steffen Jung (null) - 972WIS_INST___120Avi Stein (null)Yuval Shaked (null)Nathan Karin (null)
- Resource Type
- Journal article
- Publication Details
- PLoS ONE, Vol.7(1); Jan/2012
- Number of pages
- 10
- Language
- English
- DOI
- https://doi.org/10.1371/journal.pone.0028305
- Grant note
- Israel Cancer Research Fund (ICRF); Israel Cancer Association (ICA); Israel Ministry of Health Chief Scientist; Israel Science Foundation (ISF)This study was supported by the Israel Cancer Research Fund (ICRF), the Israel Cancer Association (ICA), the Israel Ministry of Health Chief Scientist and Israel Science Foundation (ISF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript._ALMAME_DELIMITER_
- Record Identifier
- 993265920603596
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