CRABP2 and FABP5 expression levels in diseased and normal pancreas

Autor: Christine Hughes, Joanne Chin-Aleong, Hemant M. Kocher
Rok vydání: 2020
Předmět:
0301 basic medicine
Pathology
medicine.medical_specialty
Stromal cell
endocrine system diseases
Receptors
Retinoic Acid
Retinoic acid
Fluorescent Antibody Technique
Antineoplastic Agents
Tretinoin
Fatty Acid-Binding Proteins
Fatty acid-binding protein
Pathology and Forensic Medicine
Cholangiocarcinoma
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Pancreatitis
Chronic
medicine
Biomarkers
Tumor
Humans
Pancreas
Epithelial Cells
General Medicine
Fibroblasts
medicine.disease
Survival Analysis
digestive system diseases
In vitro
Gene Expression Regulation
Neoplastic
030104 developmental biology
medicine.anatomical_structure
chemistry
Bile Duct Neoplasms
Tumor progression
Tissue Array Analysis
030220 oncology & carcinogenesis
Cancer research
Hepatic stellate cell
Disease Progression
Pancreatitis
Carcinoma
Pancreatic Ductal
Zdroj: Annals of diagnostic pathology. 47
ISSN: 1532-8198
Popis: Recently, stromal targeting, by agents such as All trans retinoic acid (ATRA), has been regarded as a promising avenue for the treatment of pancreatic ductal adenocarcinoma (PDAC). The intra-cellular transportation of ATRA to the nuclear receptors is performed by either: fatty acid binding protein 5 (FABP5) or cellular retinoic acid binding protein 2 (CRABP2), dictating the transcription of downstream genes and, thus, eventual cell phenotype. Here, we explored the levels of each protein, in pancreatic tissues of patients presenting with a range of pancreatic diseases (pancreatic ductal adenocarcinoma (PDAC), chronic pancreatitis (CP), cholangiocarcinoma (CC)). We demonstrate that there is a significantly lower CRABP2 and FABP5 expression in activated fibroblasts or pancreatic stellate cells (PSC) in PDAC, as well as other diseased pancreas as in CC and CP, versus quiescent fibroblasts. The quiescent fibroblasts consistently show a pattern of high FABP5:CRABP2 ratio, whereas PSC in all non-PDAC tissues showed a low FABP5:CRABP2 ratio. PSC in PDAC patients had a range of FABP5:CRABP2 ratios (high, even and low). There was a lower CRABP2 expression in cancerous epithelial cells (PDAC) versus normal epithelial cells. This is also present in other disease states (CP, CC). Contrasting to the patterns seen for fibroblasts, the FABP5 expression in PDAC epithelial cells matched that of the normal epithelial cells. However, the normal epithelial cells had a high FABP5:CRABP2 ratio, compared to the PDAC epithelial cells. These ratios may have correlation with tumor progression, and overall survival. These findings could be confirmed in in vitro cell lysates. CRABP2 and FABP5 levels and ratios could serve as valuable biomarkers.
Databáze: OpenAIRE
Externí odkaz: