Proteomics

Dataset Information

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Hypoxia-induced proteomic remodeling of human mammary cancer associated fibroblast - siRNA NCBP2-AS2


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. Amongst those, the uncharacterized antisense gene protein NCBP2-AS2 is one of the most transcriptionally upregulated proteins in the proteome and secretome of hypoxic CAFs. Silencing of NCBP2-AS2 abrogates the pro-angiogenic function acquired by hypoxic CAFs through decreasing VEGF expression levels to the levels found in normoxic CAFs.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Fibroblast

DISEASE(S): Breast Cancer

SUBMITTER: Sara Zanivan  

LAB HEAD: Sara Zanivan

PROVIDER: PXD006539 | Pride | 2019-02-15

REPOSITORIES: Pride

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Publications

Hypoxic cancer-associated fibroblasts increase NCBP2-AS2/HIAR to promote endothelial sprouting through enhanced VEGF signaling.

Kugeratski Fernanda G FG   Atkinson Samuel J SJ   Neilson Lisa J LJ   Lilla Sergio S   Knight John R P JRP   Serneels Jens J   Juin Amelie A   Ismail Shehab S   Bryant David M DM   Markert Elke K EK   Machesky Laura M LM   Mazzone Massimiliano M   Sansom Owen J OJ   Zanivan Sara S  

Science signaling 20190205 567


Intratumoral hypoxia causes the formation of dysfunctional blood vessels, which contribute to tumor metastasis and reduce the efficacy of therapeutic treatments. Blood vessels are embedded in the tumor stroma of which cancer-associated fibroblasts (CAFs) constitute a prominent cellular component. We found that hypoxic human mammary CAFs promoted angiogenesis in CAF-endothelial cell cocultures in vitro. Mass spectrometry-based proteomic analysis of the CAF secretome unraveled that hypoxic CAFs co  ...[more]

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