2017
DOI: 10.1016/j.celrep.2017.12.011
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Tumor-Associated Macrophages Derived from Circulating Inflammatory Monocytes Degrade Collagen through Cellular Uptake

Abstract: Summary Physiologic turnover of interstitial collagen is mediated by a sequential pathway, in which collagen is fragmented by pericellular collagenases, endocytosed by collagen receptors, and routed to lysosomes for degradation by cathepsins. Here, we used intravital microscopy to investigate if malignant tumors, which are characterized by high rates of extracellular matrix turnover, utilize a similar collagen degradation pathway. Tumors of epithelial, mesenchymal, or neural crest origin all displayed vigorous… Show more

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Cited by 117 publications
(96 citation statements)
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“…Densely cross‐linked fibrin provides a scaffold for metastatic tumor cell invasion and is associated with CD14 expression and disease progression in non‐small lung cancer patients . Mϕs derived from CCR2 + monocytes can directly degrade the ECM within tumors by endocytosing deposited collagen . Additional studies are needed to better understand how monocytes contribute to the composition and organization of tumor ECM, and whether ECM‐derived signals regulate monocyte fate in cancer.…”
Section: Functions In Cancermentioning
confidence: 99%
“…Densely cross‐linked fibrin provides a scaffold for metastatic tumor cell invasion and is associated with CD14 expression and disease progression in non‐small lung cancer patients . Mϕs derived from CCR2 + monocytes can directly degrade the ECM within tumors by endocytosing deposited collagen . Additional studies are needed to better understand how monocytes contribute to the composition and organization of tumor ECM, and whether ECM‐derived signals regulate monocyte fate in cancer.…”
Section: Functions In Cancermentioning
confidence: 99%
“…Tumor‐defying and antimetastatic property has also been attributed to MMP8, most likely derived from TANs, in murine melanoma and lung cancer models where MMP8 increased adhesion of tumor cells to ECM proteins and reduced tumor invasiveness . Collagen fragments, most likely derived from various MMP actions, are further degraded through endocytic pathways by a subset of TAMs, originating from CCR2+ monocytes in a mouse lung carcinoma model . Therefore, the dynamics of TAM/TAN‐mediated ECM remodeling dictate the fate of tumor progression in vivo.…”
Section: Tams Tans and The Tmementioning
confidence: 99%
“…148 Collagen fragments, most likely derived from various MMP actions, are further degraded through endocytic pathways by a subset of TAMs, originating from CCR2+ monocytes in a mouse lung carci-noma model. 153 Therefore, the dynamics of TAM/TAN-mediated ECM remodeling dictate the fate of tumor progression in vivo.…”
Section: Tumor-associated Hypoxia On Tam/tan Recruitmentmentioning
confidence: 99%
“…Macrophages remodel extracellular matrix (ECM) through matrix metalloproteinases (MMP) which degrade collagen and create tracks for tumor cells to migrate [31,32]. Such tracks also enable macrophages to migrate toward and interact with other cells in the TME to support tumor progression, for example by their contact-dependent support of the epithelial-to-mesenchymal transition (EMT) of tumor cell aggregates [33], or their contact with the endothelium to increase its permeability to intravasating tumor cells [34].…”
Section: Introductionmentioning
confidence: 99%