Fibroblast growth factors induce hepatic tumorigenesis post radiofrequency ablation

Fibroblast growth factors induce hepatic tumorigenesis post radiofrequency ablation

Image-guided radiofrequency ablation (RFA) is used to treat focal tumors in the liver and other organs. Despite potential advantages over surgery, hepatic RFA can promote local and distant tumor growth by activating pro-tumorigenic growth factor and cytokines. Thus, strategies to identify and suppre...

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Published in:Scientific reports Vol. 13; no. 1; p. 16341
Main Authors: Markezana, Aurelia, Paldor, Mor, Liao, Haixing, Ahmed, Muneeb, Zorde-Khvalevsky, Elina, Rozenblum, Nir, Stechele, Matthias, Salvermoser, Lukas, Laville, Flinn, Goldmann, Salome, Rosenberg, Nofar, Andrasina, Tomas, Ricke, Jens, Galun, Eithan, Goldberg, Shraga Nahum
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 28-09-2023
Nature Publishing Group
Nature Portfolio
Subjects:
631/67/1059
692/4028
Ablation
Cell culture
Colorectal cancer
Colorectal carcinoma
Cytokines
Fibroblast growth factor 2
Fibroblast growth factors
Growth factors
Hepatocellular carcinoma
Hepatocytes
Humanities and Social Sciences
Hyperthermia
Liver
Liver cancer
multidisciplinary
Protein arrays
Radiofrequency ablation
Science
Science (multidisciplinary)
Signal transduction
Thermal stress
Tissue culture
Tumor cell lines
Tumorigenesis
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Summary:Image-guided radiofrequency ablation (RFA) is used to treat focal tumors in the liver and other organs. Despite potential advantages over surgery, hepatic RFA can promote local and distant tumor growth by activating pro-tumorigenic growth factor and cytokines. Thus, strategies to identify and suppress pro-oncogenic effects of RFA are urgently required to further improve the therapeutic effect. Here, the proliferative effect of plasma of Hepatocellular carcinoma or colorectal carcinoma patients 90 min post-RFA was tested on HCC cell lines, demonstrating significant cellular proliferation compared to baseline plasma. Multiplex ELISA screening demonstrated increased plasma pro-tumorigenic growth factors and cytokines including the FGF protein family which uniquely and selectively activated HepG2. Primary mouse and immortalized human hepatocytes were then subjected to moderate hyperthermia in-vitro, mimicking thermal stress induced during ablation in the peri-ablational normal tissue. Resultant culture medium induced proliferation of multiple cancer cell lines. Subsequent non-biased protein array revealed that these hepatocytes subjected to moderate hyperthermia also excrete a similar wide spectrum of growth factors. Recombinant FGF-2 activated multiple cell lines. FGFR inhibitor significantly reduced liver tumor load post-RFA in MDR2-KO inflammation-induced HCC mouse model. Thus, Liver RFA can induce tumorigenesis via the FGF signaling pathway, and its inhibition suppresses HCC development.
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content type line 23
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-42819-2