PXD001984

PXD001984 is an original dataset announced via ProteomeXchange.

Title	Deciphering molecular consequences of the prohormone convertase 1/3 inhibition in macrophages for application in immunotherapy - Cellular Extracts
Description	The prohormone convertase 1/3 (PC1/3) is an enzyme playing an important role in the processing of precursor proteins involved in neuroimmune phenotype of neuroendocrine cells. The expression of PC1/3 is not only restricted to neuroendocrine tissues; recent studies reported a role of PC1/3 in Toll-like receptor immune response in macrophages. Here, using lentivirus strategy, we investigated the consequences of PC1/3 down-regulation with the aim of understanding the intracellular impact of such inhibition and its biological application to cancer therapy. Under sterile conditions, we demonstrated that PC1/3 inactivated macrophages express a M1-like phenotype characterized by filopodia extensions, pro-inflammatory chemokines and cytokines secretion (IL6, CXCL10; TNF) and TLR4 Myd88 dependent signaling activation. Under LPS challenge, PC1/3 KO cells secrete through store-operated calcium entry increase, a cocktail of pro-inflammatory factors including alarmins and chemokines conducting to attract naïve T helper lymphocytes (Th0) which favors cytotoxic response. Tests perform with the secreted factors by the challenged PC1/3 KO cells on breast and ovarian cancer cells (SKBR3, SKOV3) establish that the factors secreted are able to inhibit both viability and resistance to chemotherapies. Under inhibitory conditions using IL-10, the PC1/3 KO cells still continue to produce inflammatory cytokines and anti-tumoral factors. Taken together, these data establish that inhibition of PC1/3 can be used as a potential immune therapy for awaking intra-tumoral macrophages.
HostingRepository	PRIDE
AnnounceDate	2015-09-09
AnnouncementXML	Submission_2015-09-09_07:57:57.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Maxence Wisztorski
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2015-03-26 09:12:17	ID requested
⏵ 1	2015-09-09 07:57:58	announced

Duhamel M, Rodet F, Delhem N, Vanden Abeele F, Kobeissy F, Nataf S, Pays L, Desjardins R, Gagnon H, Wisztorski M, Fournier I, Day R, Salzet M, Molecular Consequences of Proprotein Convertase 1/3 (PC1/3) Inhibition in Macrophages for Application to Cancer Immunotherapy: A Proteomic Study. Mol Cell Proteomics, 14(11):2857-77(2015) [pubmed]

submitter keyword: Shotgun proteomics, macrophages

Michel Salzet
contact affiliation	Université de Lille, Sciences et Technologies - INSERM U1192 - Laboratoire PRISM, France
contact email	michel.salzet@univ-lille1.fr
lab head
Maxence Wisztorski
contact affiliation	Université Lille 1
contact email	maxence.wisztorski@univ-lille1.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD001984
     1. Label: PRIDE project
     2. Name: Deciphering molecular consequences of the prohormone convertase 1/3 inhibition in macrophages for application in immunotherapy - Cellular Extracts