Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcriptional profiling comparing S100PBP over-expressing human FA6 pancreatic cancer cells to vector-only control FA6 cells

ABSTRACT: S100PBP is significantly down-regulated in pancreatic cancer compared to normal samples. The functional roles of S100PBP are unknown, and therefore, profiling cells over-expressing this gene may lead to further understanding of its functional mechanisms. We have performed microarray gene expression analysis of FA6 cells over-expressing S100PBP to vector-only control cells to gain clues on the cellular functions of S100PBP.

ORGANISM(S): Homo sapiens

SUBMITTER: Claude Chelala

PROVIDER: E-GEOD-35198 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Similar Datasets

Project description:This study aims to elucidate the cellular mechanisms underlying the secretion of factor B (CFB), recognized for its dual role as an early biomarker of pancreatic ductal adenocarcinoma (PDAC) and as the initiating substrate for the alternative complement pathway (ACP), a crucial component of the innate immune system. Employing parallel reaction monitoring analysis, we substantiated CFB's consistent ~2-fold elevated expression in PDAC patients compared to both healthy donors (HD) and chronic pancreatitis (CP) patients, thereby affirming its status as a cancer biomarker, as previously established through ELISA methods. In contrast to CFB expression, we observed heightened ACP activity in the patients of CP and other benign cancer compared to both HD and PDAC patients, prompting further exploration of a potential functional link between ACP and PDAC. To investigate the cellular secretion mechanism of CFB, we conducted protein-protein interaction analyses involving key complement proteins and their regulatory factors within the ACP cascade. These analyses encompassed blood samples from PDAC patients spanning various disease stages, alongside cancer cell lines. Our findings unveiled an intricate control system governing the ACP and its regulatory factors, including KRAS mutation, adrenomedullin (AM), and factor H (CFH). Notably, AM emerged as a pivotal player in CFB secretion, activating CFH and thereby promoting its predominant binding to C3b over CFB. Mechanistically, our data propose that KRAS mutation stimulates AM expression, subsequently enhancing CFH activity in the fluid phase through binding. This heightened AM-CFH interaction evidently conferred a greater affinity for C3b over CFB, potentially leading to suppression of the ACP cascade. This sequence of events likely culminated in the release of ductal CFB into plasma during the early stages of PDAC. Thus, our findings illuminate an intriguing trade-off between suppressed ACP activity and the early detection of PDAC.

Dataset Information

Transcriptional profiling comparing S100PBP over-expressing human FA6 pancreatic cancer cells to vector-only control FA6 cells

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets