Proteomics

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Differential protein secretome induced by TNF-alpha


ABSTRACT: Endothelial-mesenchymal-transition (EndMT) is an important source of cancer-associated fibroblasts (CAFs), which are known to facilitate tumor progression. We have previously shown that EndMT is present in pancreatic tumors and that deficiency of the Tie1 receptor induces EndMT in human endothelial cells. Pancreatic tumors are characterized by the presence of tumor necrosis factor-α (TNF-α). We now show that TNF-α strongly induces human endothelial cells to undergo EndMT. In order to know the secretory feature of cells which undergo EndMT by TNF-α, we conducted a comparative analysis of HMVEC secretome treated or not for 24h and 48h with TNF-α. Secretome study shows that cells treated with TNF-α have an important fibroblast-like secretory capacity, and a proinflamatory signature. Moreover, Ingenuity Pathway Analysis (IPA) shows that pathways implicated in migration, inflammation and fibrosis are predicted to be activated and that necrosis and apoptosis pathways are inhibited. Accordingly cell survival, viability and cycle progression are activated. We show that TNF-α- treated cells secrete proteins related to 16 protumoral pathways, confirming their fibroblastic characteristic. Finally, among the predicted upstream regulators activated, IPA analysis shows that, TNFSF12 and its receptor are present at hight levels in PDAC patients. Altogether these results show the fibroblastic characteristic of treated cells and demonstrate that TNF-α induces CAFs.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hmvec Cell, Microvascular Endothelial Cell

SUBMITTER: Luc Camoin  

LAB HEAD: Luc Camoin

PROVIDER: PXD014488 | Pride | 2021-09-08

REPOSITORIES: pride

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Controle_24h.raw Raw
Controle_24h_170809221631.raw Raw
Controle_24h_170810005219.raw Raw
Controle_48h.raw Raw
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Publications

TNF-α induces endothelial-mesenchymal transition promoting stromal development of pancreatic adenocarcinoma.

Adjuto-Saccone Marjorie M   Soubeyran Philippe P   Garcia Julie J   Audebert Stéphane S   Camoin Luc L   Rubis Marion M   Roques Julie J   Binétruy Bernard B   Iovanna Juan Lucio JL   Tournaire Roselyne R  

Cell death & disease 20210625 7


Endothelial-mesenchymal transition (EndMT) is an important source of cancer-associated fibroblasts (CAFs), which facilitates tumour progression. PDAC is characterised by abundant CAFs and tumour necrosis factor-α (TNF-α). Here, we show that TNF-α strongly induces human endothelial cells to undergo EndMT. Interestingly, TNF-α strongly downregulates the expression of the endothelial receptor TIE1, and reciprocally TIE1 overexpression partially prevents TNF-α-induced EndMT, suggesting that TNF-α ac  ...[more]

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