Abstract
Hepatocellular carcinoma (HCC) is one of the most prevalent and deadly cancers worldwide. Therefore, current global research focuses on molecular tools for early diagnosis of HCC, which can lead to effective treatment at an early stage. Perilipin 5 (PLIN5) has been studied as one of the main proteins of the perilipin family, whose role is to maintain lipid homeostasis by inhibiting lipolysis. In this study, we show for the first time that PLIN5 is strongly expressed in tumors of human patients with HCC as well as in mouse livers, in which HCC was genetically or experimentally induced by treatment with the genotoxic agent diethylnitrosamine. Moreover, the secreted acute phase glycoprotein Lipocalin 2 (LCN2) established as a biomarker of acute kidney injury, is also proven to indicate liver injury with upregulated expression in numerous cases of hepatic damage, including steatohepatitis. LCN2 has been studied in various cancers, and it has been assigned roles in multiple cellular processes such as the suppression of the invasion of HCC cells and their metastatic abilities. The presence of this protein in blood and urine, in combination with the presence of α-Fetoprotein (AFP), is hypothesized to serve as a biomarker of early stages of HCC. In the current study, we show in humans and mice that LCN2 is secreted into the serum from liver cancer tissue. We also show that AFP-positive hepatocytes represent the main source for the massive expression of LCN2 in tumoral tissue. Thus, the strong presence of PLIN5 and LCN2 in HCC and understanding their roles could establish them as markers for diagnosis or as treatment targets against HCC.
Highlights
Perilipin 5 (PLIN5) belongs to the family of perilipins consisting of 5 distinct members (PLIN1-5), which are major structural proteins located on the surface of lipid droplets known to serve as factors for lipid homeostasis by modulating lipid storage, with crucial roles in diseases characterized with lipid manifestations [1,2]
In this study we report for the first time the presence of PLIN5 in Hepatocellular carcinoma (HCC)
The expression of PLIN5 launches in the tumor formation within HCC livers making it a promising marker for studies focusing on oncogenic effects in liver tissue
Summary
PLIN5 belongs to the family of perilipins consisting of 5 distinct members (PLIN1-5), which are major structural proteins located on the surface of lipid droplets known to serve as factors for lipid homeostasis by modulating lipid storage, with crucial roles in diseases characterized with lipid manifestations [1,2]. PLIN5 is the latest discovered member of this protein family expressed in fatty acid oxidizing tissues such as heart, liver, adipose tissue and muscle. PLIN5 mediates mitochondrial function, regulating fatty acid storage and release to maintain lipid droplet homeostasis [5,6]. Most of the studies performed on PLIN5 have focused on its function in the heart. A primary study pointed to a protective role of PLIN5 against hepatic lipotoxicity [7]
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