Selection of bone metastasis seeds by mesenchymal signals in the primary tumor stroma Journal Article

   

Authors:	Zhang, X. H. F.; Jin, X.; Malladi, S.; Zou, Y.; Wen, Y. H.; Brogi, E.; Smid, M.; Foekens, J. A.; Massague, J.
Article Title:	Selection of bone metastasis seeds by mesenchymal signals in the primary tumor stroma
Abstract:	How organ-specific metastatic traits arise in primary tumors remains unknown. Here, we show a role of the breast tumor stroma in selecting cancer cells that are primed for metastasis in bone. Cancer-associated fibroblasts (CAFs) in triple-negative (TN) breast tumors skew heterogeneous cancer cell populations toward a predominance of clones that thrive on the CAF-derived factors CXCL12 and IGF1. Limiting concentrations of these factors select for cancer cells with high Src activity, a known clinical predictor of bone relapse and an enhancer of PI3K-Akt pathway activation by CXCL12 and IGF1. Carcinoma clones selected in this manner are primed for metastasis in the CXCL12-rich microenvironment of the bone marrow. The evidence suggests that stromal signals resembling those of a distant organ select for cancer cells that are primed for metastasis in that organ, thus illuminating the evolution of metastatic traits in a primary tumor and its distant metastases. © 2013 Elsevier Inc.
Journal Title:	Cell
Volume:	154
Issue:	5
ISSN:	0092-8674
Publisher:	Cell Press
Date Published:	2013-08-29
Start Page:	1060
End Page:	1073
Language:	English
DOI:	10.1016/j.cell.2013.07.036
PROVIDER:	scopus
PUBMED:	23993096
PMCID:	PMC3974915
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84883377982&partnerID=40&md5=6266f912881962042764e2c828f5b921
Notes:	--- - Cited By (since 1996):1 - "Export Date: 1 October 2013" - "CODEN: CELLB" - "Source: Scopus"

https://synapse.mskcc.org/synapse/works/has_related_data_chk/46205