PLoS One. 2012; 7(1): e28305
Izhak L, Wildbaum G, Jung S, Stein A, Shaked Y, Karin N
The CCL2 CCR2 axis is likely to contributes to a growth as well as progression of cancer diseases by two major mechanisms; autocrine effect of CCL2 as a survival/growth cause for CCR2+ cancer cells and, a attraction of CCR2+ CX(3)CR1+tumor associated macrophages which in a absence of CCR2 frequency migrate. Thus far no in vivo system has been set up to differentiate a selective contribution of each of these facilities to cancer development. Here we employed a chimera animal indication in which all non-malignant cells have been CCR2-/-, but all cancer cells have been CCR2+, combined with an adoptive transfer system of bone marrow (BM) CX(3)CR1+ cells from CCR2+ mice harboring a targeted replacement of a CX(3)CR1gene by an enhanced green fluorescent protein (EGFP) reporter gene (cx(3)cr1(gfp)), together with a CD45.1 congene. Using this system we dissected a selective contribution of CX(3)CR1+CCR2+ cells, which comprise only about 7% of CD11b+ BM cells, to growth growth as well as angiogenesis. Showing which aside for their direct pro-angiogenic effect they have been essential for a recruitment of other CD11b+ cells to a growth site. We further show which a administration department of CCR2-Ig, which selectively as well as specifically neutralize CCL2, to mice in which CCR2 is expressed only on growth cells, further suppressed growth development, implicating for a key role of this chemokine supporting growth survival in an autocrine manner. This further emphasizes a important role of CCL2 as a aim for care of cancer diseases.
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