PXD002051

PXD002051 is an original dataset announced via ProteomeXchange.

Title	Secretome identification of immune cell factors mediating metastatic cell homing
Description	Metastatic cell homing is a complex process mediated in part by diffusible factors secreted from immune cells found at a pre-metastatic niche. We report on connecting together secretomics and a TRanscriptional Activity CEll aRray (TRACER) to identify functional paracrine interactions between immune cells and metastatic cells as novel mediators of metastatic cell homing. Splenocytes from orthotopic mouse models of breast cancer were isolated to generate a diseased splenocyte conditioned media (D-SCM) containing immune cell secreted factors. MDA-MB-231 metastatic cell activity including cell invasion, migration, transendothelial migration, and proliferation were increased when cultured with D-SCM compared to healthy SCM (H-SCM) and unconditioned media controls. Our secretome analysis of D-SCM yielded secreted factor candidates that contribute to increased metastatic cell activity. In parallel, we identified active TFs within metastatic cells in response to the secreted factors using TRACER. We connected both data sets using MetaCore software to determine interactions between immune cell secreted factors and active metastatic cell TFs to narrow down functional secreted factor candidates that mediate metastatic cell homing. Haptoglobin was among the list of secreted factors and was validated in vitro as a key mediator of metastatic cell recruitment. Furthermore, we designed an implantable poly(lactide-co-glycolide) biomaterial scaffold as a mimic of the pre-metastatic niche to slowly release haptoglobin and demonstrate increased homing of metastatic cells to the scaffold in vivo. Taken together, our studies demonstrate a novel systems biology technique to identify functional paracrine signaling factors, which were validated to reveal mediators of metastatic cell homing.
HostingRepository	PRIDE
AnnounceDate	2015-12-17
AnnouncementXML	Submission_2015-12-17_02:33:38.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dhaval Nanavati
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2015-04-13 00:28:52	ID requested
⏵ 1	2015-12-17 02:33:39	announced

Aguado BA, Wu JJ, Azarin SM, Nanavati D, Rao SS, Bushnell GG, Medicherla CB, Shea LD, Secretome identification of immune cell factors mediating metastatic cell homing. Sci Rep, 5():17566(2015) [pubmed]

curator keyword: Biomedical

submitter keyword: Mouse, LC MS/MS, secretome

Lonnie D. Shea, Ph.D
contact affiliation	Department of Biomedical Engineering University of Michigan, Ann Arbor 1119 Carl A. Gerstacker Building 2200 Bonisteel Boulevard Ann Arbor, MI 48109-2099
contact email	ldshea@umich.edu
lab head
Dhaval Nanavati
contact affiliation	Northwestern University Proteomics core
contact email	d-nanavati@northwestern.edu
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/2015/12/PXD002051

PRIDE project URI

• PRIDE
  1. PXD002051
     1. Label: PRIDE project
     2. Name: Secretome identification of immune cell factors mediating metastatic cell homing