Tumor-Associated Macrophages Promote Colorectal Tumor Development Through Remodeling of Its Extracellular Matrix

Ly6Chi monocytes massively infiltrate the CRC-tumors by virtue of their CCR2 expression and further mature into Ly6CloF4/80hi CD64hiMHCII+ TAM upon tumor progression. We demonstrated that TAM-deficient tumors display impaired tumor-growth via alternation of the ECM morphology, structure and composition. Using advanced high-resolution optical imaging to visualize the tumoral-ECM macromolecule network together with transcriptomic and proteomic approaches we unraveled that TAM play critical role in the deposition, linearization and cross-linking of collagenous ECM. Remarkably, we show that cues embedded in ECM by TAM-mediated remodeling activity promote tumor cell proliferation in vitro and orthotopic tumor development in vivo.

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Afik R, Zigmond E, Vugman M, Klepfish M, Shimshoni E, Pasmanik-Chor M, Shenoy A, Bassat E, Halpern Z, Geiger T, Sagi I, Varol C