scholarly journals Tumor-Associated Neutrophils in Hepatocellular Carcinoma Pathogenesis, Prognosis, and Therapy

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2899
Author(s):  
Konstantinos Arvanitakis ◽  
Ioannis Mitroulis ◽  
Georgios Germanidis
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Investigation ◽  
Primary Liver Cancer ◽  
Tumor Therapy ◽  
Treatment Modalities ◽  
Current Evidence ◽  
Anticancer Treatment ◽  
And Migration ◽  
Tumor Associated Neutrophils

Hepatocellular carcinoma represents the most prevalent primary liver cancer worldwide, and it is either caused by intrinsic genetic mutations or by a multitude of extrinsic risk factors. Even though the interplay between chronic inflammatory changes and hepatocarcinogenesis has been at the forefront of clinical investigation for the past few decades, the role of tumor-associated neutrophils (TANs) in HCC development still remains ambiguous. On the one hand, N1 TANs exhibit an anti-tumorigenic activity, mediated by direct or indirect tumor cell lysis, whereas on the other hand, N2 TANs have been correlated with increased HCC growth, invasiveness, and metastasis. The association of an elevated Neutrophil-to-Lymphocyte Ratio (NLR) with poor prognosis in patients with HCC, has been recently brought into spotlight, consolidating its widespread use as a reliable biomarker. Due to the decisive involvement of TANs in HCC pathogenesis and development, the utilization of various neutrophil-centered anticancer treatment modalities has been under clinical experimentation, selectively targeting and modulating the processes of neutrophil recruitment, activation, and migration. This review summarizes current evidence on the role of TANs in HCC pathogenesis and progression, as well as in their potential involvement in tumor therapy, shedding light on emerging anticancer treatment methods targeting neutrophils.

scholarly journals Tumor-Associated Macrophages in Hepatocellular Carcinoma Pathogenesis, Prognosis and Therapy

Cancers ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 226
Author(s):  
Konstantinos Arvanitakis ◽  
Triantafyllia Koletsa ◽  
Ioannis Mitroulis ◽  
Georgios Germanidis
Keyword(s):  
Hepatocellular Carcinoma ◽  
Bone Marrow ◽  
Clinical Investigation ◽  
Tumor Therapy ◽  
Treatment Modalities ◽  
Current Evidence ◽  
Tumor Associated Macrophages ◽  
Hematopoietic Stem ◽  
Anticancer Treatment

Hepatocellular carcinoma (HCC) constitutes a major health burden globally, and it is caused by intrinsic genetic mutations acting in concert with a multitude of epigenetic and extrinsic risk factors. Cancer induces myelopoiesis in the bone marrow, as well as the mobilization of hematopoietic stem and progenitor cells, which reside in the spleen. Monocytes produced in the bone marrow and the spleen further infiltrate tumors, where they differentiate into tumor-associated macrophages (TAMs). The relationship between chronic inflammation and hepatocarcinogenesis has been thoroughly investigated over the past decade; however, several aspects of the role of TAMs in HCC development are yet to be determined. In response to certain stimuli and signaling, monocytes differentiate into macrophages with antitumor properties, which are classified as M1-like. On the other hand, under different stimuli and signaling, the polarization of macrophages shifts towards an M2-like phenotype with a tumor promoting capacity. M2-like macrophages drive tumor growth both directly and indirectly, via the suppression of cytotoxic cell populations, including CD8+ T cells and NK cells. The tumor microenvironment affects the response to immunotherapies. Therefore, an enhanced understanding of its immunobiology is essential for the development of next-generation immunotherapies. The utilization of various monocyte-centered anticancer treatment modalities has been under clinical investigation, selectively targeting and modulating the processes of monocyte recruitment, activation and migration. This review summarizes the current evidence on the role of TAMs in HCC pathogenesis and progression, as well as in their potential involvement in tumor therapy, shedding light on emerging anticancer treatment methods targeting monocytes.

The oncogenic role of ARG2 in hepatocellular carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16713-e16713
Author(s):  
Pin-Jen Lin ◽  
Fang-Yen Chiu ◽  
Shu-Chi Wang ◽  
Chia-Yang Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Growth ◽  
Solid Tumor ◽  
Colony Formation ◽  
Primary Liver Cancer ◽  
Migration Ability ◽  
Poor Overall Survival ◽  
And Migration ◽  
High Level

e16713 Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer in adult and is a leading cause of cancer-related death worldwide. In most mammals, two isoforms of arginase have been identified (ARG1 and ARG2). Clinical Data revealed that ARG2 is highly expressed in various types of cancers including HCC. However, the role of ARG2 in regulating the progression of HCC has not yet been examined. The present study aimed to examine the role of ARG2 on the progression of HCC. Methods: Cell growth and proliferation were examined by MTT assay and colony formation assay, respectively. Cell migration was determined using wound-healing assay. The expression of ARG2 and its correlated survival rate in HCC was analyzed by DriverDBv3 database. Results: Our experimental results showed that knockdown of ARG2 suppresses cell growth, colony formation and migration ability in HepG2 cells. In HCC patients, ARG2 is highly expressed in primary solid tumor and recurrence solid tumor samples comparing to solid tissue normal samples. In addition, high level of ARG2 is associated with poor overall survival in HCC patients. Conclusions: These results suggest that ARG2 plays an oncogenic role in modulating HCC progression.

Knockout of Ajuba Attenuates the Growth and Migration of Hepatocellular Carcinoma Cells

2020 ◽  
Vol 160 (11-12) ◽  
pp. 650-658
Author(s):  
Yichen Le ◽  
Yi He ◽  
Meirong Bai ◽  
Ying Wang ◽  
Jiaxue Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Growth ◽  
Cancer Progression ◽  
Normal Liver ◽  
Cell Growth And Migration ◽  
And Migration ◽  
Hcc Cells

Ajuba has been found to be mutated or aberrantly regulated in several human cancers and plays important roles in cancer progression via different signaling pathways. However, little is known about the role of Ajuba in hepatocellular carcinoma (HCC). Here, we found an upregulation of Ajuba expression in HCC tissues compared with normal liver tissues, while a poor prognosis was observed in HCC patients with high Ajuba expression. Knockout of Ajuba in HCC cells inhibited cell growth in vitro and in vivo, suppressed cell migration, and enhanced the cell apoptosis under stress. Moreover, re-expression of Ajuba in Ajuba-deficient cells could restore the phenotype of Ajuba-deficient cells. In conclusion, these results indicate that Ajuba is upregulated in HCC and promotes cell growth and migration of HCC cells, suggesting that Ajuba could possibly be a new target for HCC diagnosis and treatment.

scholarly journals Modification of Epigenetic Histone Acetylation in Hepatocellular Carcinoma

Cancers ◽  
2018 ◽  
Vol 10 (1) ◽  
pp. 8 ◽  
Author(s):  
Kwei-Yan Liu ◽  
Li-Ting Wang ◽  
Shih-Hsien Hsu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Chemical Sensor ◽  
Enzyme Level ◽  
Tumor Therapy ◽  
Tumor Formation ◽  
Current Evidence ◽  
Epigenetic Changes ◽  
Suppressor Genes

Cells respond to various environmental factors such as nutrients, food intake, and drugs or toxins by undergoing dynamic epigenetic changes. An imbalance in dynamic epigenetic changes is one of the major causes of disease, oncogenic activities, and immunosuppressive effects. The aryl hydrocarbon receptor (AHR) is a unique cellular chemical sensor present in most organs, and its dysregulation has been demonstrated in multiple stages of tumor progression in humans and experimental models; however, the effects of the pathogenic mechanisms of AHR on epigenetic regulation remain unclear. Apart from proto-oncogene activation, epigenetic repressions of tumor suppressor genes are involved in tumor initiation, procession, and metastasis. Reverse epigenetic repression of the tumor suppressor genes by epigenetic enzyme activity inhibition and epigenetic enzyme level manipulation is a potential path for tumor therapy. Current evidence and our recent work on deacetylation of histones on tumor-suppressive genes suggest that histone deacetylase (HDAC) is involved in tumor formation and progression, and treating hepatocellular carcinoma with HDAC inhibitors can, at least partially, repress tumor proliferation and transformation by recusing the expression of tumor-suppressive genes such as TP53 and RB1.

scholarly journals Biological and Clinical Significance of the CCR5/CCL5 Axis in Hepatocellular Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 883 ◽  
Author(s):  
Santosh K. Singh ◽  
Manoj K. Mishra ◽  
Brian M. Rivers ◽  
Jennifer B. Gordetsky ◽  
Sejong Bae ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Clinical Significance ◽  
Treatment Options ◽  
Biological Significance ◽  
Improve Patient Survival ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Despite the improvement in survival for patients with liver cancer (LCa) in recent decades, only one in five patients survive for 5 years after diagnosis. Thus, there is an urgent need to find new treatment options to improve patient survival. For various cancers, including LCa, the chemokine CCL5 (RANTES) facilitates tumor progression and metastasis. Since the function of the CCR5/CCL5 interaction in LCa cell proliferation and migration is poorly understood, the present study was undertaken to investigate the role of the CCR5/CCL5 axis in these processes. Flow cytometry, RT-PCR, Western blot, and immunofluorescence techniques were used to quantify the expression of CCR5 and CCL5 in LCa cells. To determine the biological significance of CCR5 expressed by LCa cell lines, a tissue microarray of LCas stained for CCR5 and CCL5 was analyzed. The results showed higher expression (p < 0.001) of CCR5 and CCL5 in hepatocellular carcinoma (HCC) tissues compared to non-neoplastic liver tissues. Furthermore, to delineate the role of the CCR5/CCL5 interaction in LCa cell proliferation and migration, various LCa cells were treated with maraviroc, a CCR5 antagonist, in the presence of CCL5. These data demonstrated the biological and clinical significance of the CCR5/CCL5 axis in LCa progression. The targeting of this axis is a promising avenue for the treatment of LCa.

scholarly journals Platelets as Key Factors in Hepatocellular Carcinoma

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1022 ◽  
Author(s):  
Natasa Pavlovic ◽  
Bhavna Rani ◽  
Pär Gerwins ◽  
Femke Heindryckx
Keyword(s):  
Hepatocellular Carcinoma ◽  
Crucial Role ◽  
Primary Liver Cancer ◽  
Organ Damage ◽  
Potential Effect ◽  
Key Factors ◽  
Therapeutic Value ◽  
Key Factor ◽  
Proliferation And Invasion

Hepatocellular carcinoma (HCC) is a primary liver cancer that usually develops in the setting of chronic inflammation and liver damage. The hepatic microenvironment plays a crucial role in the disease development, as players such as hepatic stellate cells, resident liver macrophages (Kupffer cells), endothelial cells, extracellular matrix, and a variety of immune cells interact in highly complex and intertwined signaling pathways. A key factor in these cross-talks are platelets, whose role in cancer has gained growing evidence in recent years. Platelets have been reported to promote HCC cell proliferation and invasion, but their involvement goes beyond the direct effect on tumor cells, as they are known to play a role in pro-fibrinogenic signaling and the hepatic immune response, as well as in mediating interactions between these factors in the stroma. Anti-platelet therapy has been shown to ameliorate liver injury and improve the disease outcome. However, platelets have also been shown to play a crucial role in liver regeneration after organ damage. Therefore, the timing and microenvironmental setting need to be kept in mind when assessing the potential effect and therapeutic value of platelets in the disease progression, while further studies are needed for understanding the role of platelets in patients with HCC.

Liver Transplantation for Hepatocellular Carcinoma: An Update

2006 ◽  
Vol 4 (8) ◽  
pp. 762-767 ◽  
Author(s):  
Jean F. Botha ◽  
Alan N. Langnas
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Selection Criteria ◽  
Hepatic Cirrhosis ◽  
The United States ◽  
Treatment Modalities ◽  
Hepatic Malignancy ◽  
The Third ◽  
Small Hcc

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide and the most common primary hepatic malignancy. It arises on a background of hepatic cirrhosis in approximately 95% of the cases in the United States. A wide variety of treatment modalities have been applied in the treatment of HCC. Liver transplantation has emerged as the preferred treatment for patients with small HCC. Transplantation for patients whose tumors do not exceed the Milan criteria yields results equivalent to those of transplantation for non-HCC indications. Controversy now exists regarding the use of living donors, expansion of selection criteria, and role of adjuvant therapy.

scholarly journals Unique Biological Activity and Potential Role of Monomeric Laminin-γ2 as a Novel Biomarker for Hepatocellular Carcinoma: A Review

2019 ◽  
Vol 20 (1) ◽  
pp. 226 ◽  
Author(s):  
Hiroshi Yasuda ◽  
Masatoshi Nakagawa ◽  
Hirofumi Kiyokawa ◽  
Eisaku Yoshida ◽  
Toru Yoshimura ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Biological Activities ◽  
Diagnostic Value ◽  
Cancer Surveillance ◽  
Highly Sensitive ◽  
Digestive Cancers ◽  
Chemiluminescent Immunoassay ◽  
And Migration

Laminin (Ln)-332 consists of α3, β3, and γ2 chains, which mediate epithelial cell adhesion to the basement membrane. Ln-γ2, a component of Ln-332, is frequently expressed as a monomer in the invasion front of several types of malignant tissues without simultaneous expression of Ln-α3 and/or Ln-β3 chains. Moreover, monomeric Ln-γ2 induces tumor cell proliferation and migration in vitro. These unique biological activities indicate that monomeric Ln-γ2 could be a candidate biomarker for early cancer surveillance. However, the present immune method for monomeric Ln-γ2 detection can only predict its expression, since no antibody that specifically reacts with monomeric γ2, but not with heterotrimeric γ2 chain, is commercially available. We have, therefore, developed monoclonal antibodies to specifically detect monomeric Ln-γ2, and devised a highly sensitive method to measure serum monomeric Ln-γ2 levels using a fully automated chemiluminescent immunoassay (CLIA). We evaluated its diagnostic value in sera from patients with several digestive cancers, including hepatocellular carcinoma (HCC), and found serum monomeric Ln-γ2 to be a clinically available biomarker for HCC surveillance. The combination of monomeric Ln-γ2 and prothrombin induced by Vitamin K Absence II (PIVKA-II) may be more sensitive for clinical diagnosis of HCC than any currently used combination.

scholarly journals The Role of NSAIDs in Breast Cancer Prevention and Relapse: Current Evidence and Future Perspectives

Breast Care ◽  
2016 ◽  
Vol 11 (5) ◽  
pp. 339-344 ◽  
Author(s):  
Demetrios Moris ◽  
Michalis Kontos ◽  
Eleftherios Spartalis ◽  
Ian S. Fentiman
Keyword(s):  
Breast Cancer ◽  
Cancer Prevention ◽  
Large Scale ◽  
Clinical Investigation ◽  
Breast Cancer Incidence ◽  
Breast Cancer Prevention ◽  
Current Evidence ◽  
Dose Frequency ◽  
Chemopreventive Agents

Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) have received considerable interest as potential chemopreventive agents. The aim of this review is to summarize the accumulated knowledge on the effect of NSAIDs on breast cancer incidence and natural history, and the underlying pathophysiology. NSAIDs mainly block inflammation by inhibiting cyclooxygenase enzymes, leading to lower prostaglandin synthesis. The latter has been reported to affect breast cancer risk through hormonal and inflammation-related pathways. Intensity, dose, frequency, duration, and timing of administration may also be significant. There is currently enough evidence to support a role of NSAIDs in breast cancer prevention and relapse, which deserves further large-scale experimental and clinical investigation.

scholarly journals Knockdown of SLC34A2 Inhibits Hepatocellular Carcinoma Cell Proliferation and Invasion

2016 ◽  
Vol 24 (6) ◽  
pp. 511-519 ◽  
Author(s):  
Yanhua Li ◽  
Xia Chen ◽  
Hong Lu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Underlying Mechanism ◽  
Mesenchymal Transition ◽  
Human Carcinomas ◽  
And Migration ◽  
Proliferation And Invasion ◽  
Hcc Cells

The gene solute carrier family 34 (sodium phosphate), member 2 (SLC34A2), is a member of the SLC34 family. Increasing evidence suggests that SLC34A2 is involved in the development of many human carcinomas. However, its role in hepatocellular carcinoma (HCC) is still unclear. Therefore, in this study we investigated the role of SLC34A2 in HCC and explored the underlying mechanism. We found that the expression of SLC34A2 is upregulated in HCC cell lines. Knockdown of SLC34A2 obviously inhibited HCC cell proliferation, migration/invasion, and the epithelial‐mesenchymal transition (EMT) phenotype. Furthermore, knockdown of SLC34A2 significantly inhibited the expression of phosphorylated PI3K and AKT in HCC cells. Taken together, these results suggest that knockdown of SLC34A2 inhibits proliferation and migration by suppressing activation of the PI3K/AKT signaling pathway in HCC cells, and SLC34A2 may be a potential therapeutic target for the treatment of HCC.

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