PXD002094

PXD002094 is an original dataset announced via ProteomeXchange.

Title	Tumor-Associated Macrophages Promote Colorectal Tumor Development Through Remodeling of Its Extracellular Matrix
Description	Extracellular matrix (ECM) structural and compositional abnormalities are a hallmark of many cancers. Tumor associated macrophages (TAM) are considered pivotal players in mounting pro-tumoral functions; yet, their role in tumor-ECM remodeling remains largely ambiguous. Using an orthotopic murine model of colorectal cancer we defined two major CRC TAM subsets arising from Ly6Chi monocytes recruited in a CCR2-depedent manner. TAM-deficient CRC tumors established Ccr2-/- mice exhibited attenuated growth. Advanced imaging techniques revealed that the enhanced deposition, linearization and cross-linking of collagen fibers typical to tumor growth were absent in the Ccr2-/- tumors. Moreover, the Ccr2-/- tumors displayed altered ECM composition with 348 proteins that were differentially expressed in comparison with WT tumors, among them 46 were ECM related. Integrating transcriptomic and proteomic approaches we defined a TAM signature of ECM remodeling enzymes, structural and affiliated proteins. Specifically, were prominent proteins involved with the synthesis and assembly of collagen type I, IV and XIV. Finally, decellularized 3D ECM fragments extracted from WT tumors, but not from Ccr2-/- tumors or upstream healthy colon, enhanced tumor cell proliferation in vitro and tumor development in the native colonic environment. Collectively, our integrated biophysical-immunologic-omic approaches uncover new mechanistic insights of TAM-mediated remodeling of tumor ECM structure and composition.
HostingRepository	PRIDE
AnnounceDate	2016-09-26
AnnouncementXML	Submission_2016-10-14_04:11:07.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tamar Geiger
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2015-04-21 01:51:58	ID requested
1	2016-09-26 08:13:03	announced
⏵ 2	2016-10-14 04:11:08	announced	Updated publication reference for PubMed record(s): 27697834.

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, Tumor macrophages are pivotal constructors of tumor collagenous matrix. J Exp Med, 213(11):2315-2331(2016) [pubmed]

curator keyword: Biomedical

submitter keyword: Tumor-associated macrophages, Murine CRC model, Colorectal cancer, Extracellular matrix, Tumor microenvironment

Dr. Tamar Geiger
contact affiliation	Sackler Faculty of Medicine Tel Aviv University
contact email	geiger@tauex.tau.ac.il
lab head
Tamar Geiger
contact affiliation	Tel Aviv University
contact email	geiger@tauex.tau.ac.il
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2016/09/PXD002094

PRIDE project URI

• PRIDE
  1. PXD002094
     1. Label: PRIDE project
     2. Name: Tumor-Associated Macrophages Promote Colorectal Tumor Development Through Remodeling of Its Extracellular Matrix