Monocyte Trafficking in Tumor Metastasis

Monocytes trafficking into primary tumors and their metastases were studied by adoptive transfer of mouse (Ly6C/Gr1⁺ or Ly6C/Gr1⁻) or human (CD14+CD16+ and CD16−) monocytes using MMTV-PyMT autochthonous, human and mouse experimental metastasis and human orthotopic tumor models. Monocytes and macrophages were recovered by enzymatic disaggregation of the tumors followed by FACS analysis. To test mechanisms behind monocyte recruitment and the effect of inhibition of this trafficking on metastasis anti-mouse or human neutralizing CCL2 antibodies or Ccr2 null mutant mice were used. In order to ablate VEGF expression in monocytes a myeloid specific (Csf1r promoter) tamoxifen inducible Cre expressing strain was crossed with VEGF^flox/flox mice and gene ablation induced by tamoxifen. Effects of monocyte depletion on tumor cell extravasation using Met-1, a FVB PyMT tumor derived metastatic cell line, was determined using an ex vivo intact lung imaging system and an in vitro extravasation assay.

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Qian B.Z., Li J., Zhang H., Kitamura T., Zhang J., Campion L.R., Kaiser E.A., Snyder L.A, & Pollard J.W. (2011). CCL2 recruits inflammatory monocytes to facilitate breast tumor metastasis. Nature, 475(7355), 222-225.

Publication 2011

Adoptive transfer Assay Ccl2 Cell Csf1r Enzymatic Gene Human Inhibition Lung Macrophages Metastasis Mice Mmtv Monocyte Neutralizing antibodies Null mice Strain Tamoxifen Tumor Tumor cell line Vegf

Corresponding Organization :

Other organizations : Albert Einstein College of Medicine

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Variable analysis

independent variables

Adoptive transfer of mouse (Ly6C/Gr1+ or Ly6C/Gr1−) or human (CD14+CD16+ and CD16−) monocytes
Anti-mouse or human neutralizing CCL2 antibodies
Ccr2 null mutant mice
Tamoxifen-induced ablation of VEGF expression in monocytes (using myeloid-specific Csf1r promoter Cre expressing strain crossed with VEGFflox/flox mice)

dependent variables

Monocyte and macrophage recovery from tumors by enzymatic disaggregation and FACS analysis
Effects of monocyte depletion on tumor cell extravasation (using Met-1 FVB PyMT tumor-derived metastatic cell line) determined using ex vivo intact lung imaging system and in vitro extravasation assay

control variables

Not explicitly mentioned

controls

Positive control: Not specified
Negative control: Not specified

Annotations

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