PXD021457

PXD021457 is an original dataset announced via ProteomeXchange.

Title	Critical role of Aquaporin-1 and telocytes in infantile hemangioma response to propranolol beta-blockade
Description	Propranolol, a non-selective β-adrenergic receptor (ADRB) antagonist, is the first-line therapy for severe infantile hemangiomas (IH). Since the incidental discovery of propranolol efficacy in IH, preclinical and clinical investigations have shown evidence of adjuvant propranolol response in some malignant tumors. However, the mechanism for propranolol antitumor effect is still largely unknown, owing to the absence of a tumor model responsive to propranolol at non-toxic concentrations. Immunodeficient mice engrafted with different human tumor cell lines were treated with anti-VEGF bevacizumab, to create a model sensitive to propranolol. Proteomics analysis was used to reveal propranolol-mediated protein alteration correlating with tumor growth inhibition and Aquaporin-1 (AQP1), a water channel modulated in tumor cell migration and invasion, was identified. IH tissues and cells were then functionally investigated. Our functional protein association networks analysis and knockdown of ADRB2 and AQP1 indicated that propranolol treatment and AQP1 downregulation trigger the same pathway, suggesting that AQP1 is a major driver of betablockers antitumor response. Examining AQP1 in human hemangioma samples, we found it exclusively in a perivascular layer, so far unrecognized in IH, made of telocytes (TC). Functional in vitro studies showed that AQP1-positive telocytes play a critical role in IH response to propranolol and that modulation of AQP1 in IH-TC by propranolol or shAQP1 decreases capillary-like tube formation in a Matrigel based angiogenesis assay. We conclude that IH sensitivity to propranolol may rely at least in part to a cross talk between lesional vascular cells and stromal telocytes.
HostingRepository	PRIDE
AnnounceDate	2021-01-25
AnnouncementXML	Submission_2021-01-25_00:00:26.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stephane Claverol
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-14 02:07:23	ID requested
⏵ 1	2021-01-25 00:00:26	announced

Dataset with its publication pending

submitter keyword: Hemangioma

propranolol

telocyte

aquaporin-1

angiogenesis.

Bonneu M.
contact affiliation	Proteome Platform, University of Bordeaux, F-33076, Bordeaux, France.
contact email	marc.bonneu@gmail.com
lab head
Stephane Claverol
contact affiliation	Plateforme Proteome
contact email	stephane.claverol@u-bordeaux.fr
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/2021/01/PXD021457

PRIDE project URI

• PRIDE
  1. PXD021457
     1. Label: PRIDE project
     2. Name: Critical role of Aquaporin-1 and telocytes in infantile hemangioma response to propranolol beta-blockade