Expression profile of adrenomedullin and its specific receptors in liver tissues from patients with hepatocellular carcinoma and in tumorigenic cell line-secreted extracellular vesicles.

Autor: Cabiati M; CNR Institute of Clinical Physiology, Pisa, Italy. Electronic address: manuela.cabiati@ifc.cnr.it., Gaggini M; CNR Institute of Clinical Physiology, Pisa, Italy. Electronic address: mgaggini@ifc.cnr.it., De Simone P; Hepatobiliary surgery and liver transplantation, University of Pisa Medical School Hospital, Pisa, Italy. Electronic address: p.desimone@ao-pisa.toscana.it., Salvadori C; CNR Institute of Clinical Physiology, Pisa, Italy. Electronic address: costanzasalvadori@yahoo.it., Del Turco S; CNR Institute of Clinical Physiology, Pisa, Italy. Electronic address: delturco@ifc.cnr.it., Caselli C; CNR Institute of Clinical Physiology, Pisa, Italy. Electronic address: caselli@ifc.cnr.it., Cecchettini A; CNR Institute of Clinical Physiology, Pisa, Italy; Hepatobiliary surgery and liver transplantation, University of Pisa Medical School Hospital, Pisa, Italy. Electronic address: antonella.cecchettini@unipi.it., Del Ry S; CNR Institute of Clinical Physiology, Pisa, Italy. Electronic address: delry@ifc.cnr.it.
Jazyk: angličtina
Zdroj: Pathology, research and practice [Pathol Res Pract] 2023 Mar; Vol. 243, pp. 154383. Date of Electronic Publication: 2023 Feb 20.
DOI: 10.1016/j.prp.2023.154383
Abstrakt: The transcriptional profile of adrenomedullin (AM), a new metastasis-related factor involved in hepatocellular carcinoma (HCC), and its specific receptors (CLR, RAMP1, RAMP3) were evaluated in liver tissues of HCV-positive HCC subjects undergoing liver transplantation (LR) and in donors (LD). AM and its specific receptor expression were also assessed in extracellular vesicles (EVs) secreted by tumorigenic (HepG2) and non-tumorigenic (WRL68) cells by Real-Time PCR. AM expression resulted significantly elevated in LR concerning LD (p = 0.0038) and, for the first time, significantly higher levels in HCC patients as a function of clinical severity (MELD score), were observed. RAMP3 and CLR expression increased in LR as a function of clinical severity while RAMP1 decreased. Positive correlations were found among AM, its receptors, and apoptotic markers. No AM mRNA expression difference was observed between HepG2 and WRL68 EVs. RAMP1 and RAMP3 resulted lower in HepG2 concerning WRL68 while significantly higher levels were observed for CLR. While results at tissue level characterize AM as a regulator of carcinogenesis-tumor progression, those obtained in EVs do not indicate AM as a target candidate, neither as a pathological biomarker nor as a marker involved in cancer therapy.
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Databáze: MEDLINE