PXD008956

PXD008956 is an original dataset announced via ProteomeXchange.

Title	STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis
Description	The brain microenvironment imposes a particularly intense selective pressure on metastasis initiating cells, but successful metastasis bypass this control through mechanisms that are poorly understood. Reactive astrocytes are key components of this microenvironment, as they have been observed to confine brain metastasis without infiltrating the lesion. We describe a subpopulation of reactive astrocytes surrounding metastatic lesions that are characterized by the activation of STAT3 pathway. Blocking STAT3 signaling in this subpopulation of reactive astrocytes reduces experimental brain metastasis from different primary tumor sources, even at advanced stages of colonization. We conclude that brain metastatic cells induce and maintain the co-option of a pro-metastatic program driven by STAT3 in a subpopulation of reactive astrocytes. We also show that a safe and orally bioavailable treatment that inhibits STAT3 in patients with established brain metastasis and extracranial disease exhibits significant antitumor effects, especially in the CNS where several complete responses were achieved. Given that brain metastasis imposes significant morbidity and mortality, our experimental results suggest a novel treatment for increasing survival in patients with secondary brain tumors.
HostingRepository	PRIDE
AnnounceDate	2018-07-16
AnnouncementXML	Submission_2018-07-16_04:03:52.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Javier Munoz
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	maXis

Revision	Datetime	Status	ChangeLog Entry
0	2018-02-14 02:01:03	ID requested
⏵ 1	2018-07-16 04:03:53	announced

Priego N, Zhu L, Monteiro C, Mulders M, Wasilewski D, Bindeman W, Doglio L, Mart, í, nez L, Mart, í, nez-Saez E, Ram, ó, n Y Cajal S, Meg, í, as D, Hern, á, ndez-Encinas E, Blanco-Aparicio C, Mart, í, nez L, Zarzuela E, Mu, ñ, oz J, Fustero-Torre C, Pi, ñ, eiro-Y, á, ñ, ez E, Hern, á, ndez-La, í, n A, Bertero L, Poli V, Sanchez-Martinez M, Menendez JA, Soffietti R, Bosch-Barrera J, Valiente M, STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis. Nat Med, 24(7):1024-1035(2018) [pubmed]

curator keyword: Biomedical

submitter keyword: brain metastasis, secretome, stat3, astrocytes

Javier Munoz
contact affiliation	Spanish National Cancer Research Center (CNIO)
contact email	jmunozpe@cnio.es
lab head
Javier Munoz
contact affiliation	CNIO
contact email	jmunozpe@cnio.es
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/2018/07/PXD008956

PRIDE project URI

• PRIDE
  1. PXD008956
     1. Label: PRIDE project
     2. Name: STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis