Prognostic role of galectins expression in patients with hepatic cancer

Shao, Qing; He, Jin; Chen, Zhiming; Wu, Changping

doi:10.1097/md.0000000000019622

Cited by 13 publications

(9 citation statements)

References 32 publications

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“…In cohorts of patients with HCC, the high Gal-1 expression in HCC tumor cells has been largely proven to be a poor prognostic factor after tumor resection, significantly associated with poor OS ( Wu et al, 2012 , 2018 ; Shao et al, 2020 ). However, the Gal-1 expression in TAMs has seldom been investigated, and, to the best of our knowledge, our study is the first to demonstrate its clinical significance in HCC.…”

Section: Discussionmentioning

confidence: 99%

Autophagy Drives Galectin-1 Secretion From Tumor-Associated Macrophages Facilitating Hepatocellular Carcinoma Progression

Davuluri

Chen

Chiu

et al. 2021

Front. Cell Dev. Biol.

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Galectin-1 (Gal-1) is a secretory lectin with pro-tumor activities and is associated strongly with hepatocellular carcinoma (HCC) development. Although Gal-1 is a well-known soluble pro-tumor factor in the tumor microenvironment (TME), the secretion mode of Gal-1 is not clearly defined. On the other hand, in addition to cancer cells, Gal-1 is widely expressed in tumor stromal cells, including tumor-associated macrophages (TAMs). TAMs are a significant component of stromal cells in TME; however, their contributions in producing Gal-1 to TME are still not explored. Here we reveal that TAMs can actively secrete Gal-1 in response to stimuli of HCC cells. Gal-1 produced by TAMs leads to an increase of the systemic level of Gal-1 and HCC tumor growth in mice. Mechanistically, TLR2-dependent secretory autophagy is found to be responsible for Gal-1 secretion from TAMs. Gal-1 acts as a cargo of autophagosomes to fuse with multivesicular bodies via Rab11 and VAMP7-mediated vesicle trafficking before being secreted. This autophagy-regulated Gal-1 secretion in TAMs correlates to poor overall survival and progression-free survival rates of HCC patients. Our findings uncover the secretion mode of Gal-1 via secretory autophagy and highlight the pathological role of TAM-produced Gal-1 in HCC progression.

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Section: Discussionmentioning

confidence: 99%

Autophagy Drives Galectin-1 Secretion From Tumor-Associated Macrophages Facilitating Hepatocellular Carcinoma Progression

Davuluri

Chen

Chiu

et al. 2021

Front. Cell Dev. Biol.

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“…Galectin-3 is known to affect HCC cell apoptosis, adhesion, migration, angiogenesis, and inflammatory responses, making it a possible tumor marker in HCC [6]. Also, it was discovered to be associated with worse prognosis in HCC patients [7,8] and it can be a target for new therapies for HCC [9,10].…”

Section: Introductionmentioning

confidence: 99%

Galectin-3 is not useful for hepatocellular carcinoma surveillance in cirrhotic patients but it may be a marker of cirrhosis development

Nassar¹,

Elkalbashawy²,

Kamal³

et al. 2021

ceh

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Aim of the study: Ultrasound surveillance for hepatocellular carcinoma (HCC) among cirrhotic patients is the currently used modality but it is operator dependent. Combining a tumor marker with ultrasound may improve sensitivity for early HCC detection. Our aim was to assess the galectin-3 level among HCC and cirrhotic patients on top of chronic hepatitis C to evaluate its possible role as a tumor marker for HCC surveillance among cirrhotic patients. Material and methods: The study was conducted on 160 subjects. They were grouped as follows: group 1: 40 patients with HCC secondary to liver cirrhosis on top of chronic hepatitis C; group 2: 40 patients with cirrhosis secondary to chronic hepatitis C; group 3: 40 patients with chronic hepatitis C without advanced fibrosis; group 4: 40 healthy controls. Serum galectin-3 levels were determined in all subjects using ELISA. Results: Serum galectin-3 level was significantly higher in HCC patients than in those with chronic hepatitis C (p < 0.001). Also it was significantly higher among cirrhotic patients than in patients with chronic hepatitis C (p < 0.001). But on comparing HCC patients with cirrhotic patients, serum galectin-3 levels were not significantly different (p = 0.926). Conclusions: Galectin-3 levels cannot be used as an additional method for surveillance of HCC among cirrhotic patients.

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“…Galectin-1, being a 14 kDa beta-galactose specific binding protein [55], is known to be increased in numerous neoplasms, including primary hepatic tumors [56]. Moreover, Galectin-1 is a negative prognostic marker in HCC [57,58]. And finally, Galectin-1 has been linked to the PI3K-AKT-mTOR signaling, thereby enhancing epithelial-mesenchymal-transition (EMT) in HCC cell lines [59].…”

Section: Resultsmentioning

confidence: 99%

RASSF1A independence and early Galectin-1 upregulation in PIK3CA induced hepatocarcinogenesis: new therapeutic venues

Scheiter

Evert

Reibenspies

et al. 2021

Preprint

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Aberrant activation of the PI3K/AKT/mTOR and Ras/Mitogen-Activated Protein Kinase pathways is a hepatocarcinogenesis hallmark. In a subset of hepatocellular carcinomas (HCC), PI3K/AKT/mTOR signaling dysregulation depends on PIK3CA mutations, while RAS/MAPK activation is partly attributed to promoter methylation of the tumor suppressor RASSF1A. To evaluate a possible co-carcinogenic effect of PIK3CA activation and RASSF1A knockout, plasmids expressing oncogenic forms of PIK3CA (E545K or H1047R mutants) were delivered to the liver of RASSF1A knockout and wildtype mice by hydrodynamic tail vein injection combined with Sleeping Beauty-mediated somatic integration. Transfection of either PIK3CA E545K or H1047R mutants sufficed to induce hepatocellular carcinomas in mice irrespective of RASSF1A mutational background. The related tumors displayed a lipogenic phenotype with upregulation of Fatty acid synthase and Stearoyl-CoA desaturase-1 (SCD1). Galectin 1, which was commonly upregulated in preneoplastic lesions and tumors, emerged as a regulator of SCD1. Co-inhibitory treatment with PIK3CA inhibitors and the Galectin 1 inhibitor OTX-008 resulted in synergistic cytotoxicity in human HCC cell lines, suggesting novel therapeutic venues.

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Prognostic role of galectins expression in patients with hepatic cancer

Cited by 13 publications

References 32 publications

Autophagy Drives Galectin-1 Secretion From Tumor-Associated Macrophages Facilitating Hepatocellular Carcinoma Progression

Autophagy Drives Galectin-1 Secretion From Tumor-Associated Macrophages Facilitating Hepatocellular Carcinoma Progression

Galectin-3 is not useful for hepatocellular carcinoma surveillance in cirrhotic patients but it may be a marker of cirrhosis development

RASSF1A independence and early Galectin-1 upregulation in PIK3CA induced hepatocarcinogenesis: new therapeutic venues

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