Hypoxia-induced proteomic remodeling of human mammary cancer associated fibroblast

ABSTRACT: Intratumoral hypoxia causes the formation of dysfunctional blood vessels which contribute to tumor metastasis. Blood vessels are embedded in the tumor stroma where cancer-associated fibroblasts (CAFs) constitute the most prominent cellular component. We found that hypoxic human mammary CAFs promote blood vessel growth in CAF-endothelial cell co-cultures in vitro. Mass spectrometry-based proteomic analysis of CAF secretome unravels how hypoxic CAFs contribute to blood vessel abnormalities by altering the secretion of a multitude of pro- and anti-angiogenic factors. Hypoxia induces pronounced remodeling of the CAF proteome, including proteins that have not been previously related to this process. Our study provides a map of unprecedented depth of hypoxia-induced molecular alterations in mammary CAFs that can be exploited to identify novel mechanisms that control hypoxic CAF functions.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Fibroblast

DISEASE(S): Breast Cancer

SUBMITTER: Sara Zanivan  

LAB HEAD: Sara Zanivan

PROVIDER: PXD006535 | Pride | 2019-02-15

REPOSITORIES: Pride