Abstract
Background: Fibroblast growth factor 21 (FGF21) is a protein produced primarily by hepatocytes in response to metabolic stress and acts both locally and systemically. It leads to positive physiological changes including weight loss, improved glycaemic control and reduction in hepatic fat and is shown to be protective against hepatocellular carcinoma and pancreatic cancer in mice. It is a target in clinical trials for metabolic disorders including non-alcoholic steatohepatitis and type 2 diabetes.
Purpose: To determine the expression of FGF21 in a range of normal human tissues and malignant tumours.
Method: A novel anti-FGF21 polyclonal antibody was generated in collaboration with Vertebrate Antibodies Ltd and validated by ELISA and immunoblot prior to optimisation for immunohistochemistry (IHC) on formalin fixed wax embedded tissue. IHC was performed on a human multi tissue/tumour microarray accessed via Grampian Biorepository (ethics no TR00161) using Agilent Dako Autostainer with primary antibody at a dilution of 1 in 75. Liver was considered a positive control. Tissue cores were reviewed by two independent observers.
Results: The antibody successfully detected FGF21 in formalin fixed wax embedded normal human liver with localisation to hepatocytes. FGF21 was also detectable in gastric mucosa, adrenal cortex, pancreatic islet cells, renal tissue and placenta. Tumours expressing FGF21 were sarcoma/GIST, squamous cell carcinoma and hepatocellular carcinoma, the latter reduced compared to non-diseased liver.
Conclusion: This study confirms the presence of FGF21 within hepatocytes and also demonstrates the expression of FGF21 in other tissues and tumours most notably tissue with endocrine functions (pancreatic islet cells, renal, adrenal cortex and placenta) and squamous cell carcinoma and sarcoma/GIST. The role of FGF21 in these tissues warrants further investigation and as FGF21 is an emerging therapeutic target, a more robust understanding of its patho-physiological roles is essential.
Purpose: To determine the expression of FGF21 in a range of normal human tissues and malignant tumours.
Method: A novel anti-FGF21 polyclonal antibody was generated in collaboration with Vertebrate Antibodies Ltd and validated by ELISA and immunoblot prior to optimisation for immunohistochemistry (IHC) on formalin fixed wax embedded tissue. IHC was performed on a human multi tissue/tumour microarray accessed via Grampian Biorepository (ethics no TR00161) using Agilent Dako Autostainer with primary antibody at a dilution of 1 in 75. Liver was considered a positive control. Tissue cores were reviewed by two independent observers.
Results: The antibody successfully detected FGF21 in formalin fixed wax embedded normal human liver with localisation to hepatocytes. FGF21 was also detectable in gastric mucosa, adrenal cortex, pancreatic islet cells, renal tissue and placenta. Tumours expressing FGF21 were sarcoma/GIST, squamous cell carcinoma and hepatocellular carcinoma, the latter reduced compared to non-diseased liver.
Conclusion: This study confirms the presence of FGF21 within hepatocytes and also demonstrates the expression of FGF21 in other tissues and tumours most notably tissue with endocrine functions (pancreatic islet cells, renal, adrenal cortex and placenta) and squamous cell carcinoma and sarcoma/GIST. The role of FGF21 in these tissues warrants further investigation and as FGF21 is an emerging therapeutic target, a more robust understanding of its patho-physiological roles is essential.
| Original language | English |
|---|---|
| Pages (from-to) | S63 |
| Number of pages | 1 |
| Journal | Journal of Pathology |
| Volume | 261 |
| Issue number | S1 |
| DOIs | |
| Publication status | Published - 16 Nov 2023 |
