Proteomics approach unravels early changes in Human Fibro-blasts-Pancreatic Ductal Adenocarcinoma cells crosstalk

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a leading causes of cancer mortality worldwide. Non-specific symptoms, lack of biomarkers in the early stages, and drug resistance due to the presence of a dense fibrous stroma all contribute to poor outcome of this disease. The extracellular matrix of PDAC is secreted by activated fibroblasts known as cancer associated fibroblasts (CAFs). These fibroblasts can also affect cancer cell aggressiveness by paracrine crosstalk with cancer and immune cells present inside the tumor mass. The interplay among tumoral cells, immune cells and CAFs involve a huge array of molecules especially cytokines. Given the importance of CAFs in PDAC pathology it is critical to recognize the mechanisms involved in the crosstalk between these cells. To this aim, we first identified the proteins released from the pancreatic cancer cell line MIA-PaCa2 by proteomic analysis of their conditioned medium (CM). Second, fibroblasts were treated with MIA-PaCa2 CM for 24 and 48 hours and their proteostatic changes were detected by proteomics. Pathway analysis indicated that fi-broblasts treated with CM undergo changes compatible with the activation of migra-tion, vasculogenesis, cellular homeostasis and metabolism of ammino acids and re-duced apoptosis. These biological activities are possibly regulated by ITGB3 and TGFB1/2 in an early stage (24 hours) while SMAD3 and STAT3 could be the key player at later times (48 hours). In conclusion this study shed light on the crosstalk between PDAC cells and associated fibroblasts.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Fibroblast

DISEASE(S): Pancreatic Ductal Adenocarcinoma

SUBMITTER: Maria Concetta Cufaro  

LAB HEAD: Damiana Pieragostino

PROVIDER: PXD030974 | Pride | 2022-05-20

REPOSITORIES: Pride