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Tumor-associated macrophages derived from circulating inflammatory monocytes degrade collagen through cellular uptake

ABSTRACT: Physiologic turnover of interstitial collagen is mediated by a sequential pathway, in which collagen is fragmented by pericellular collagenases, endocytosed by specific collagen receptors, and routed to lysosomes for degradation by lysosomal 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 endocytic collagen degradation with an abundance of cells engaged in this process. These cells were identified as tumor-associated macrophage (TAM)-like cells that degraded collagen in a mannose receptor-dependent manner. Accordingly, increased intra-tumoral collagen was observed in mannose receptor-deficient mice. Whole transcriptome profiling uncovered a distinct extracellular matrix-catabolic signature of these collagen-degrading TAMs. Lineage-ablation studies revealed that collagen-degrading TAMs originated from circulating CCR2+ monocytes. The study identifies a novel function of TAMs in altering the tumor microenvironment through endocytic collagen turnover and establishes macrophages as centrally engaged in tumor-associated collagen degradation.

ORGANISM(S): Mus musculus

PROVIDER: GSE107053 | GEO | 2018/01/01

SECONDARY ACCESSION(S): PRJNA418920

REPOSITORIES: GEO

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Cathepsin K Contributes to Cavitation and Collagen Turnover in Pulmonary Tuberculosis

Project description:Cavitation in tuberculosis (TB) enables highly efficient person-to-person aerosol transmission. Currently, a number of hypotheses exist regarding the mechanisms underlying this process. To explore this process, we undertook an unbiased next-generation transcriptional analysis of samples from cavity walls, grossly normal tissue from the same lung, and uninfected control lungs. Of 17,318 mapped host transcripts, only 199 showed a significant >2-fold change in cavity wall versus normal infected and uninfected samples. Amongst 22 upregulated proteases, 5 type I collagenases were over-represented; these included cathepsin K (CTSK), mast cell chymase-1 (CMA1), matrix metalloproteinase (MMP)-1, MMP-13, and MMP-14. To determine if cavitation was associated with changes in collagen turnover, we assayed serum and urinary markers of collagen metabolism in rabbits with cavitary TB versus infected controls. Serum collagen type 1 C-terminal propeptide (CICP, a marker of collagen synthesis and degradation) and urinary deoxypyridinoline (DPD, a marker of degradation) were increased by 10- (p = 0.019) and 4-fold (p = 0.068), respectively; while urinary helical peptide (a marker of degradation) was decreased 3-fold (p=0.015). This indicates that cavitation in TB is associated with significant increases of both destruction and synthesis of collagen and that cleavage of type I collagen occurs outside the known cleavage sites of MMP-1, -13 and -14. Rabbit gene expression analysis in lung tissue from M. tuberculosis infected animals. Cavitary tissue, non cavitary tissue and lung tissue from non-infected animals are compared.

2015-11-03 | E-GEOD-68206 | biostudies-arrayexpress

Cathepsin K Contributes to Cavitation and Collagen Turnover in Pulmonary Tuberculosis

2015-11-03 | GSE68206 | GEO

Secretomic analysis of a novel strain SM1988

Project description:Strain SM1988T is a Gram-negative, aerobic, oxidase- and catalase-positive, unipolar flagellated, and rod-shaped bacterium capable of hydrolyzing casein, gelatin and collagens. Phylogenetic analysis revealed that strain SM1988T formed a distinct phylogenetic lineage along with known genera within the family Pseudoalteromonadaceae, with 16S rRNA gene sequence similarity being less than 93.3% to all known species in the family. Based on the phylogenetic, genomic, chemotaxonomic and phenotypic data, strain SM1988T was considered to represent a novel species in a novel genus in the family Pseudoalteromonadaceae, for which the name Flocculibacter collagenilyticus gen. nov., sp. nov. is proposed, with the type strain being SM1988T (= MCCC 1K04279T = KCTC 72761T). Strain SM1988T showed a high production (236 U/mL) of extracellular collagenases, which had high activity against both bovine collagen and codfish collagen. Biochemical tests combined with genomic and secretomic analyses indicated that the collagenases secreted by strain SM1988T are serine proteases from the S8 family. These data suggest that strain SM1988T acts as an important player in marine collagen degradation and recycling and may have a promising potential in collagen resource utilization.

2021-01-14 | PXD023431 | Pride

RNA Sequencing Analysis of the gonadal adipose tissue and liver from PEP Wild Type, heterozygotes and knock out mice.

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Distinct Combinatorial Events Generated by ECM Degradation Dictate Cell Behavior

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2016-11-08 | GSE79749 | GEO

Autophagy mediates degradation of nuclear lamina

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2015-10-08 | GSE63440 | GEO

Distinct Combinatorial Cascade of Events Generated by ECM Proteolysis Dictates Cell Behavior

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2016-09-27 | PXD003553 | Pride

Spatial proteomics defines the content of trafficking vesicles captured by golgin tethers

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2020-12-01 | PXD018110 | Pride

Enzymes degraded under high light maintain proteostasis by transcriptional regulation in Arabidopsis

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2022-01-19 | GSE131545 | GEO

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