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PXD008384

PXD008384 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMicro-metastases regression following primary tumor excision: a critical role for primary tumor secretome
DescriptionNumerous 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:13:07.461.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterTamar Geiger
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02017-12-07 03:11:37ID requested
12020-10-06 22:33:29announced
22024-10-22 05:13:07announced2024-10-22: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
curator keyword: Biomedical
submitter keyword: Human, Breast Cancer, LC-MS, Cancer Microenvironment, Secretome, Metastasis
Contact List
Doctor Tamar Geiger
contact affiliationDepartment of Human Molecular Genetics and Biochemistry Sackler Faculty of Medicine Tel Aviv University Israel
contact emailgeiger@tauex.tau.ac.il
lab head
Tamar Geiger
contact affiliationWeizmann Institute of Science
contact emailgeiger@tauex.tau.ac.il
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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