PXD008384-2

PXD008384 is an original dataset announced via ProteomeXchange.

Title	Micro-metastases regression following primary tumor excision: a critical role for primary tumor secretome
Description	Numerous case studies have reported spontaneous regression of metastases following tumor excision, but underlying mechanisms are elusive. Here we present a model of metastases regression and latency elicited by the removal of a primary tumor, and identify underlying mechanisms. Human breast cancer cells, expressing highly sensitive luciferase, were implanted into the mammary fat-pad of mice, and the progression of early stage micrometastases, was monitored. Upon establishment of micrometastases, the primary tumor was excised, inducing a robust regression of metastatic signal, resulting in latent foci. In vivo supplementation of tumor secretome immediately upon tumor excision diminished this regression, implicating primary tumor secreted factors in promotion of metastatic growth. In vitro, cancer cell conditioned medium reduced apoptosis and enhanced adhesion of non-confluent cancer cells, and induced angiogenesis in endothelial cells. Cytokine array and proteomic analysis of cancer cells secretome identified 359 extracellular secreted factors, with significant enrichment of angiogenic factors, growth factors activity, focal adhesion, apoptosis, and metalloprotease processes. In vivo blockade of four key potential mediators of these processes, IL-8, PDGFaa, Serpin E1 (PAI-1), and MIF, arrested development of micrometastases. Moreover, high protein levels of these four factors were correlated with poor patient outcome. These results demonstrate regression and latency of metastases following tumor excision and a crucial role for primary tumor secretome in promoting early metastatic stages, suggesting novel mechanisms to control minimal residual disease.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:13:07.461.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tamar Geiger
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-12-07 03:11:37	ID requested
1	2020-10-06 22:33:29	announced
⏵ 2	2024-10-22 05:13:07	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

curator keyword: Biomedical

submitter keyword: Human, Breast Cancer, LC-MS, Cancer Microenvironment, Secretome, Metastasis

Doctor Tamar Geiger
contact affiliation	Department of Human Molecular Genetics and Biochemistry Sackler Faculty of Medicine Tel Aviv University Israel
contact email	geiger@tauex.tau.ac.il
lab head
Tamar Geiger
contact affiliation	Weizmann Institute of Science
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/2020/10/PXD008384

PRIDE project URI

• PRIDE
  1. PXD008384
     1. Label: PRIDE project
     2. Name: Micro-metastases regression following primary tumor excision: a critical role for primary tumor secretome