Angiopoietin-like protein 3 and 4 expression 4 and their serum levels in hepatocellular carcinoma

El‐Shal, Amal S.; Zidan, Haidy E.; Rashad, Nearmeen M.; Wadea, Fady M.

doi:10.1016/j.cyto.2017.03.006

Cited by 39 publications

(31 citation statements)

References 39 publications

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“…Consistent with our observation, previous studies reported higher circulating ANGPTL4 levels in patients with HCC than in those with chronic hepatitis alone and healthy controls 24 , 25 . Li et al 24 demonstrated that HCC patients with intrahepatic metastasis and macrovascular invasion have higher serum ANGPTL4 levels than those without these features, suggesting a possible role of ANGPTL4 in HCC progression.…”

Section: Discussionsupporting

confidence: 93%

Association of pro-inflammatory soluble cytokine receptors early during hepatocellular carcinoma stereotactic radiotherapy with liver toxicity

Zhao

Wang

et al. 2020

npj Precis. Onc.

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Plasma levels of soluble factors early during hepatocellular carcinoma (HCC) stereotactic body radiotherapy (SBRT) were evaluated in relation to radiation liver injury, tumor response, and risk of early death. No significant differences were found in baseline plasma levels of AFP, CXCL1, and HGF amongst HCC patients with different Child Pugh scores. Higher levels of sTNFRII (P < 0.001), and lower levels of sCD40L (P < 0.001) and CXCL1 (P = 0.01) following one to two fractions of SBRT were noted in patients who developed liver toxicity vs. those who did not. High circulating levels of AFP (HR 2.16, P = 0.04), sTNFRII (HR 2.27, P = 0.01), and sIL-6R (HR 1.99, P = 0.03) early during SBRT were associated with increased risk of death 3 months post treatment. Plasma levels of the studied factors early during SBRT were not associated with tumor response. A pro-inflammatory systemic environment is associated with development of liver toxicity and increased risk of early death following SBRT.

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Section: Discussionsupporting

confidence: 93%

Association of pro-inflammatory soluble cytokine receptors early during hepatocellular carcinoma stereotactic radiotherapy with liver toxicity

Zhao

Wang

et al. 2020

npj Precis. Onc.

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“…In cancer, release of cANGPTL4 by tumor cells induces tumor growth, venous invasion, and metastasis (4). In addition, a role of cANGPTL4 as a diagnostic and/or prognostic marker of cancer progression has been proposed for different solid tumors, including colon cancer (25), gastric cancer (26), breast cancer (27), prostate cancer (28), hepatocellular carcinoma (29,30), head and neck squamous cell carcinoma (31-34), Kaposi's sarcoma (21,35), and renal cell carcinoma (36,37).…”

Section: Resultsmentioning

confidence: 99%

Angiopoietin-like 4 binds neuropilins and cooperates with VEGF to induce diabetic macular edema

Sodhi

Ma²,

Menon³

et al. 2019

Journal of Clinical Investigation

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“…In the liver, ANGPTL4 expression has been found to be associated with cancer cell extravasation, enhanced tumorigenesis, and poor prognosis (25). In patients with HCC, serum ANGPTL4 levels correlate with tumor progression and metastasis (25,26). In contrast, ANGPTL4 expression A, Phase-contrast photographs, Western blot analysis of ERK and P-ERK, numbers of Spheres after seeding of 1 Â 10 5 cells, and LDH release for viability assessment of HepaRG-Spheres (n ¼ 3).…”

Section: Discussionmentioning

confidence: 99%

Retrodifferentiation of Human Tumor Hepatocytes to Stem Cells Leads to Metabolic Reprogramming and Chemoresistance

et al. 2019

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Human hepatocellular carcinoma (HCC) heterogeneity promotes recurrence and therapeutic resistance. We recently demonstrated that inflammation favors hepatocyte retrodifferentiation into progenitor cells. Here, we identify the molecular effectors that induce metabolic reprogramming, chemoresistance, and invasiveness of retrodifferentiated HCC stem cells. Spheroid cultures of human HepaRG progenitors (HepaRG-Spheres), HBG-BC2, HepG2, and HuH7 cells and isolation of side population (SP) from HepaRG cells (HepaRG-SP) were analyzed by transcriptomics, signaling pathway analysis, and evaluation of chemotherapies. Gene expression profiling of HepaRG-SP and HepaRG-Spheres revealed enriched signatures related to cancer stem cells, metastasis, and recurrence and showed that HepaRG progenitors could retrodifferentiate into an immature state. The transcriptome from these stem cells matched that of proliferative bad outcome HCCs in a cohort of 457 patients. These HCC stem cells expressed high levels of cytokines triggering retrodifferentiation and displayed high migration and invasion potential. They also showed changes in mitochondrial activity with reduced membrane potential, low ATP production, and high lactate production. These changes were, in part, related to angiopoietin-like 4 (ANGPTL4)induced upregulation of pyruvate dehydrogenase kinase 4 (PDK4), an inhibitor of mitochondrial pyruvate dehydrogenase. Upregulation of ANGPTL4 and PDK4 paralleled that of stem cells markers in human HCC specimens. Moreover, the PDK4 inhibitor dichloroacetate reversed chemoresistance to sorafenib or cisplatin in HCC stem cells derived from four HCC cell lines. In conclusion, retrodifferentiated cancer cells develop enhanced invasion and therapeutic resistance through ANGPTL4 and PDK4. Therefore, restoration of mitochondrial activity in combination with chemotherapy represents an attractive therapeutic approach in HCC. Significance: Restoring mitochondrial function in human hepatocellular carcinomas overcomes cancer resistance.

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Angiopoietin-like protein 3 and 4 expression 4 and their serum levels in hepatocellular carcinoma

Cited by 39 publications

References 39 publications

Association of pro-inflammatory soluble cytokine receptors early during hepatocellular carcinoma stereotactic radiotherapy with liver toxicity

Association of pro-inflammatory soluble cytokine receptors early during hepatocellular carcinoma stereotactic radiotherapy with liver toxicity

Angiopoietin-like 4 binds neuropilins and cooperates with VEGF to induce diabetic macular edema

Retrodifferentiation of Human Tumor Hepatocytes to Stem Cells Leads to Metabolic Reprogramming and Chemoresistance

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