Gas6 as a Putative Noninvasive Biomarker of Hepatic Fibrosis

Bellan, Mattia; Pogliani, Gabriele; Marconi, Cecilia; Minisini, Rosalba; Franzosi, L.; Alciato, Federica; Magrì, Andrea; Avanzi, Gian Carlo; Pirisi, Mario; Sainaghi, Pier Paolo

doi:10.2217/bmm-2016-0210

Cited by 25 publications

(21 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In consequence, HCC progression should be subsequently attenuated by diminished Gas6/Axl signaling. However, serum Gas6 levels are increased in patients with advanced fibrosis and cirrhosis as well as in HCC patients, suggesting that excess Gas6 is able to overcome the feedback inhibition of sAxl [73,130], albeit, these data have to be confirmed in larger patient cohorts. In HCC, there is not only a positive correlation of serum Gas6 and sAxl levels with increased tumor staging, but there might be even an excess of Gas6 levels compared to sAxl [131].…”

Section: Axl Receptor Shedding: Gas6-dependent Signaling Versus Simentioning

confidence: 99%

Dynamics of Axl Receptor Shedding in Hepatocellular Carcinoma and Its Implication for Theranostics

Holstein

Binder

Mikulits

2018

IJMS

View full text Add to dashboard Cite

Signaling of the receptor tyrosine kinase Axl and its ligand Gas6 is crucially involved in the development of liver fibrosis and hepatocellular carcinoma (HCC) by activation of hepatic stellate cells and modulation of hepatocyte differentiation. Shedding of Axl’s ectodomain leads to the release of soluble Axl (sAxl), which is increased in advanced fibrosis and in early-to-late stage HCC in the presence and absence of cirrhosis. Here, we focus on the dynamics of Axl receptor shedding and delineate possible scenarios how Axl signaling might act as driver of fibrosis progression and HCC development. Based on experimental and clinical data, we discuss the consequences of modifying Axl signaling by sAxl cleavage, as well as cellular strategies to escape from antagonizing effects of Axl shedding by the involvement of the hepatic microenvironment. We emphasize a correlation between free Gas6 and free sAxl levels favoring abundant Gas6/Axl signaling in advanced fibrosis and HCC. The raised scenario provides a solid basis for theranostics allowing the use of sAxl as an accurate diagnostic biomarker of liver cirrhosis and HCC, as well as Axl receptor signaling for therapeutic intervention in stratified HCC patients.

show abstract

Section: Axl Receptor Shedding: Gas6-dependent Signaling Versus Simentioning

confidence: 99%

Dynamics of Axl Receptor Shedding in Hepatocellular Carcinoma and Its Implication for Theranostics

Holstein

Binder

Mikulits

2018

IJMS

View full text Add to dashboard Cite

show abstract

“…The diagnostic accuracy was comparable to that of liver elastography. 46 Of note, Gas6 is also able to predict one of the most relevant complications of liver cirrhosis, esophageal varices. 47 …”

Section: Growth Arrest-specific 6 (Gas6)mentioning

confidence: 99%

Candidate Biomarkers of Liver Fibrosis: A Concise, Pathophysiology-oriented Review

Bellan¹,

Castello²,

Pirisi³

2018

Journal of Clinical and Translational Hepatology

Self Cite

View full text Add to dashboard Cite

Repair of sustained liver injury results in fibrosis (i.e. the accumulation of extracellular matrix proteins), and ultimately the complete distortion of parenchymal architecture of the liver, which we call cirrhosis. Detecting and staging of fibrosis is thus a mainstay in the management of chronic liver diseases, since many clinically relevant decisions, such as starting treatment and/or monitoring for complications including hepatocellular carcinoma, may depend on it. The gold standard for fibrosis staging is liver biopsy, the role of which, however, is questioned nowadays because of cost, hazards and poor acceptance by patients. On the other hand, imaging techniques and/or measurement of direct and indirect serum markers have not proved to be completely satisfactory under all circumstances as alternatives to liver biopsy. Making progress in this field is now more crucial than ever, since treatments for established fibrosis appear on the horizon. Fine dissection of the pathways involved in the pathophysiology of liver diseases has put forward several novel candidate biomarkers of liver fibrosis, such as growth arrest-specific6, Mac-2-binding protein, osteopontin, placental growth factor, growth/differentiation factor 15 and hepatocyte growth factor. All molecules have been suggested to have potential to complement or substitute methods currently used to stage liver diseases. Here, we review the pros and cons for their use in this setting.

show abstract

“…In vivo, Gas6 promotes peribronchial fibrosis in allergic airway disease (11,12) and the genetic absence of Gas6 has been shown to prevent liver inflammation and fibrosis in mice (13). Although Gas6 has emerged as a clinically relevant biomarker of liver fibrosis (14) and targeting this mediator is a promising therapeutic strategy in this disease (15)(16)(17), the role of Gas6/TAM receptors has not been investigated previously in IPF.…”

mentioning

confidence: 99%

Targeting of TAM Receptors Ameliorates Fibrotic Mechanisms in Idiopathic Pulmonary Fibrosis

Espíndola

Habiel

Narayanan

et al. 2018

Am J Respir Crit Care Med

View full text Add to dashboard Cite

show abstract

Gas6 as a Putative Noninvasive Biomarker of Hepatic Fibrosis

Abstract: Gas6 is a novel biomarker of liver fibrosis, with a potential clinical and pathophysiological relevance.

Cited by 25 publications

References 32 publications

Dynamics of Axl Receptor Shedding in Hepatocellular Carcinoma and Its Implication for Theranostics

Dynamics of Axl Receptor Shedding in Hepatocellular Carcinoma and Its Implication for Theranostics

Candidate Biomarkers of Liver Fibrosis: A Concise, Pathophysiology-oriented Review

Targeting of TAM Receptors Ameliorates Fibrotic Mechanisms in Idiopathic Pulmonary Fibrosis

Contact Info

Product

Resources

About