scholarly journals The multifaceted role of podoplanin expression in hepatocellular carcinoma

2017 ◽  
Author(s):  
Andreea Cioca ◽  
Amalia R. Ceausu ◽  
Irina Marin ◽  
Marius Raica ◽  
Anca M. Cimpean
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Cells ◽  
Tumor Invasion ◽  
Vascular Invasion ◽  
Histological Grade ◽  
Lymphatic Vessels ◽  
Cancer Associated Fibroblasts ◽  
Tissue Sections ◽  
Podoplanin Expression

The role of podoplanin in hepatocellular carcinoma (HCC) is not clear yet. The aim of our study was to evaluate the expression of podoplanin in HCC and to determine its role in hepatocarcinogenesis. We performed immunohistochemistry with monoclonal D2-40 antibody, on paraffin-embedded tissue sections of 72 patients diagnosed with HCC. Lymphatic vessels density (LVD) was increased in patients who had vascular invasion at the time of diagnosis (P=0.018) and in those with associated cirrhosis (P=0.006). Tumor cells showing podoplanin expression were correlated with histological grade (P=0.040). Podoplanin-expressing cancer associated fibroblasts (CAFs) were correlated with both LVD (P=0.019) and tumor cells (P=0.015). Our results sustain the dual role of podoplanin in HCC by its involvement in both HCC tumorigenesis, lymphatic neovascularization and tumor invasion invasiveness. A possible crosstalk between epithelial and stromal tumor cells in HCC tumor microenvironment may be mediated by podoplanin, but this hypothesis needs further studies to elucidate this interrelation.

Vascular Invasion and Herniation by Hepatocellular Carcinoma in Cirrhosis: A Wolf in Sheep's Clothing?

2005 ◽  
Vol 129 (5) ◽  
pp. 639-644 ◽  
Author(s):  
Alberto Quaglia ◽  
Nazanin Etessami ◽  
Rosalind Sim ◽  
John Difford ◽  
A. P. Dhillon
Keyword(s):  
Hepatocellular Carcinoma ◽  
Vascular Invasion ◽  
Thrombus Formation ◽  
Smooth Muscle Actin ◽  
Point Of View ◽  
Factor Xiiia ◽  
Tissue Sections ◽  
Prognostic Feature ◽  
Vascular Structures ◽  
Hematoxylin Eosin

Abstract Context.—Vascular invasion is an important diagnostic and prognostic feature of hepatocellular carcinoma (HCC) in cirrhosis. Intravascular free-floating tumor clusters (IvCs) of HCC are found histologically in the vicinity of HCC. Thrombus formation is not seen morphologically in association with these IvCs, which are usually covered by endothelium. Objective.—Our hypothesis is that these IvCs are the result of a nondestructive form of vascular invasion by HCC, and we tried to define this aspect of microvascular invasion more accurately. Design.—Tissue sections were stained with hematoxylin-eosin, and consecutive sections were stained for fibrin (Martius scarlet blue, fibrinogen), platelets (factor XIIIa), smooth muscle actin, and endothelium (CD34). We studied cirrhotic livers removed at transplantation between 1997 and 1999. Of the livers studied, 35 of 81 consecutive cirrhotic livers contained HCC, and 17 showed microscopic vascular invasion. Five of these 17 cases showed IvCs and were subjected to the study. Main Outcome Measure.—Presence or absence of thrombus formation in association with IvC. Results.—Usually, IvCs were covered by endothelium, and no associated thrombus formation was seen. In 1 case of HCC, thrombus formation was seen focally in association with disruption of the endothelial coating. Conclusions.—We propose that the endothelial-lined trabecular structure of HCC everts, frondlike, via vascular structures within the tumor capsule into peritumoral vascular lumens without destruction of the endothelial coating. This may protect these HCC tumor projections from thrombus formation but may also act as a barrier to tumor extravasation, and this may be exploited from a therapeutic point of view.

scholarly journals Understanding the Role of Fibroblasts following a 3D Tumoroid Implantation for Breast Tumor Formation

2021 ◽  
Vol 8 (11) ◽  
pp. 163
Author(s):  
Girdhari Rijal
Keyword(s):  
Tumor Cells ◽  
Breast Tumor ◽  
Tumor Tissue ◽  
Review Paper ◽  
Cell Activity ◽  
Tumor Formation ◽  
Cancer Associated Fibroblasts ◽  
Technical Challenge ◽  
Signaling Systems

An understanding of the participation and modulation of fibroblasts during tumor formation and growth is still unclear. Among many speculates, one might be the technical challenge to reveal the versatile function of fibroblasts in tissue complexity, and another is the dynamics in tissue physiology and cell activity. The histology of most solid tumors shows a predominant presence of fibroblasts, suggesting that tumor cells recruit fibroblasts for breast tumor growth. In this review paper, therefore, the migration, activation, differentiation, secretion, and signaling systems that are associated with fibroblasts and cancer-associated fibroblasts (CAFs) after implantation of a breast tumoroid, i.e., a lab-generated tumor tissue into an animal, are discussed.

scholarly journals Immunohistochemical Expression of Epidermal Growth Factor Receptor in Hepatocellular Carcinoma

PRILOZI ◽  
2018 ◽  
Vol 39 (2-3) ◽  
pp. 21-28
Author(s):  
Dafina Nikolova ◽  
Viktorija Chalovska ◽  
Magdalena Genadieva Ivanova ◽  
Emilija Nikolovska ◽  
Ance Volkanovska ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tumor Cells ◽  
Liver Tissue ◽  
Vascular Invasion ◽  
Tumor Tissue ◽  
Growth Factor Receptor ◽  
Epidermal Growth

Abstract Introduction: Epidermal growth factor receptor (EGFR) signaling plays an important role in various cancers, including hepatocellular carcinoma (HCC). We aimed to evaluate immunoexpression of EGFR in HCC and surrounding non-tumor liver tissue and to correlate it to multiple clinicopathologic data. Material and Methods: We analyzed 60 patients with HCC for multiple clinicopathologic characteristics and survival. Presence of the immunosignal and the percentage of positive tumor cells at the whole tumor tissue sample and adjacent cirrhotic liver tissue were semi-quantitatively determined. Results: Nineteen patients (31.67%) were female and 41 (68.33%) were male ranging in age from 31 to 85 years, median 61.88±10.51. Mean survival time for female patients was 8.86±1.76 months, for male 13.03±1.50 months and overall survival was 11.6051±1.19 months. The most patients had: T2 status (41.67%), no enlarged lymph nodes (90%), vascular invasion (63.33%) and well differentiated (43.33%) tumors. EGFR immunoexpression was determined in range from 0% to 100% in both tumor and non-tumor tissue with mean value of 39.58% in tumor and 86.86% in cirrhotic tissue (p<0.00). Higher percent of tumor EGFR positive cells were found in cases with higher T status, higher levels of AFP and poorly differentiated carcinoma, but not significantly. Lower percent of tumor EGFR positive cells were found in patients with vascular invasion and enlarged lymph nodes, but also not significantly. EGFR expression in tumor tissue significantly influenced survival of the patients (p<0.05). Conclusion: The study showed that expression of EGFR in lower percentage of tumor cells was associated to favorable prognosis, making it a potential prognostic marker and therapeutic target.

scholarly journals Induction of Proteases in Peritoneal Carcinomatosis, the Role of ICAM-1/CD43 Interaction

2007 ◽  
Vol 2 ◽  
pp. 117727190700200 ◽  
Author(s):  
Nawar A. Alkhamesi ◽  
Gretta Roberts ◽  
Paul Ziprin ◽  
David H. Peck ◽  
Ara W. Darzi
Keyword(s):  
Tumor Cells ◽  
Tumor Invasion ◽  
Direct Contact ◽  
Therapeutic Option ◽  
Gelatin Zymography ◽  
Cell Types ◽  
Vital Role ◽  
Indirect Contact ◽  
Clinical Issue

Introduction The development of peritoneal metastases is a significant clinical issue in the treatment of abdominal cancers and is associated with poor prognosis. We have previously shown that ICAM-1-CD43 interaction plays a significant role in tumor adhesion. However, an invasive phenotype is critical to establish tumor progression via cell associated and secreted proteases including matrix metalloproteinases. High metalloproteinases level significantly enhanced metastasis phenotype on tumors, a detrimental effect on surgical outcome. We investigated the role of direct and indirect signaling between the mesothelium and the tumor cells in enhancing tumor invasion and possible therapeutic intervention. Methods Mesothelial cells were enzymatically derived from human omental tissue and implanted in 24 wells plates. Colorectal cancer cells were then introduced and allowed a direct and an indirect contact with the mesothelial layer. Anti-ICAM antibodies, anti-CD43 antibodies, and heparin were used to block MMP production. Gelatin zymography was performed on the supernatant to detect MMPs activity. Results MMP production was observed in mesothelial and tumor cells. Direct contact between cell types enhanced MMP9 and 2 (p < 0.05). Indirect contact also stimulate MMPs but at a lower degree. ICAM-1 blocking antibodies attenuated MMP production in direct contact to that observed in the indirect. Heparin introduction achieved a similar outcome. Conclusions ICAM-1-CD43 interaction plays a vital role in tumor cells-peritoneum adhesion and invasion, which is manifested by the increased production of MMPs leading to tumor invasion and peritoneal loco-regional. Blocking this interaction with heparin can provide a new therapeutic option.

scholarly journals Serum miR-335 Level is Associated with the Treatment Response to Trans-Arterial Chemoembolization and Prognosis in Patients with Hepatocellular Carcinoma

2015 ◽  
Vol 37 (1) ◽  
pp. 276-283 ◽  
Author(s):  
Liming Cui ◽  
Yue Hu ◽  
Bin Bai ◽  
Shide Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Outcome ◽  
Molecular Marker ◽  
Treatment Response ◽  
Vascular Invasion ◽  
Healthy Controls ◽  
Lower Serum ◽  
Serum Microrna ◽  
Arterial Chemoembolization

Aim: To identify the role of serum MicroRNA-335 (miR-335) in determining the treatment response to Trans-arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) and their prognosis after TACE. Methods: A total of 125 HCC patients were enrolled in this study. All these patients underwent TACE and the treatment response was evaluated. All patients were followed for prognosis analyses. Serum miR-335 levels immediate before and 30 days after TACE were determined. Results: HCC patients had significantly lower miR-335 levels than hepatitis patients and healthy controls. Lower serum miR-335 levels were closely associated with more progressive clinical features, including a higher mean serum AFP level, more vascular invasion, cirrhosis and larger tumor size. Response rates were higher in patients with high miR-335 compared to those with low miR-335 level. Patients with lower serum miR-335 levels had significantly poorer prognosis than patients with higher serum miR-335 levels. Conclusion: Our data suggest that serum miR-335 can be used as a molecular marker to predict the treatment response and clinical outcome in HCC patients receiving TACE.

scholarly journals The Role of Fibrosis and Liver-Associated Fibroblasts in the Pathogenesis of Hepatocellular Carcinoma

2019 ◽  
Vol 20 (7) ◽  
pp. 1723 ◽  
Author(s):  
Jacopo Baglieri ◽  
David Brenner ◽  
Tatiana Kisseleva
Keyword(s):  
Hepatocellular Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Associated Fibroblasts ◽  
Hepatic Inflammation ◽  
Therapeutic Approaches ◽  
Chronic Liver Injury ◽  
Mesenchymal Transition ◽  
Liver Fibrogenesis ◽  
Tumor Growth And Invasion

Hepatocellular carcinoma (HCC) is one of the most aggressive types of cancer and lacks effective therapeutic approaches. Most HCC develops in the setting of chronic liver injury, hepatic inflammation, and fibrosis. Hepatic stellate cells (HSCs) and cancer-associated fibroblasts (CAFs) are key players in liver fibrogenesis and hepatocarcinogenesis, respectively. CAFs, which probably derive from HSCs, activate into extracellular matrix (ECM)-producing myofibroblasts and crosstalk with cancer cells to affect tumor growth and invasion. In this review, we describe the different components which form the HCC premalignant microenvironment (PME) and the tumor microenvironment (TME), focusing on the liver fibrosis process and the biology of CAFs. We will describe the CAF-dependent mechanisms which have been suggested to promote hepatocarcinogenesis, such as the alteration of ECM, CAF-dependent production of cytokines and angiogenic factors, CAF-dependent reduction of immuno-surveillance, and CAF-dependent promotion of epithelial-mesenchymal transition (EMT). New knowledge of the fibrosis process and the role of CAFs in HCC may pave the way for new therapeutic strategies for liver cancer.

scholarly journals Cancer-Associated Fibroblasts Promote Vascular Invasion of Hepatocellular Carcinoma via Downregulating Decorin-integrin β1 Signaling

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaobo Zheng ◽  
Peng Wang ◽  
Li Li ◽  
Jing Yu ◽  
Chune Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Vascular Invasion ◽  
Poor Prognosis ◽  
Cancer Associated Fibroblasts ◽  
Integrin Β1 ◽  
Primary Tumors ◽  
Invasion And Migration ◽  
Tumor Tissues ◽  
And Migration

Hepatocellular carcinoma (HCC) is a common malignancy worldwide, and the high ratio of recurrence and metastasis remains the main cause of its poor prognosis. Vascular invasion of HCC includes microvascular invasion (MVI) and portal vein tumor thrombosis (PVTT) and is regarded as a common roadmap of intrahepatic metastasis in HCC. However, the molecular mechanism underlying vascular invasion of HCC is largely unknown. Here, we analyzed the transcriptomes of primary tumors, PVTT tissues, and tumor tissues with or without MVI. We found that extracellular matrix-related pathways were involved in vascular invasion of HCC and that decorin secreted by cancer-associated fibroblasts was gradually downregulated from normal to tumor tissues and more so in PVTT tissues. We also established that low-level decorin expression is an independent risk factor for MVI and it is associated with a poor prognosis. Decorin downregulated integrin β1 and consequently inhibited HCC cell invasion and migration in vitro. Co-staining DCN and integrin β1 revealed that DCN dynamically regulated integrin β1 protein expression. Integrin β1 knockdown significantly inhibited HCC invasion and migration, and decorin combined with such knockdown synergistically augmented the anti-metastatic effects. Co-IP assay confirmed the direct interaction of decorin with integrin β1. Our findings showed that targeting cancer-associated fibroblast-related decorin is not only a promising strategy for inhibiting HCC vascular invasion and metastasis but also provides insight into the clinical treatment of patients with PVTT.

Tumor microenvironment acid-sensitive liposomes enhanced colorectal cancer therapy by acting on both tumor cells and cancer-associated fibroblasts

Nanoscale ◽  
2021 ◽  
Author(s):  
chenglei li ◽  
Zhaohuan Li ◽  
Xue Gong ◽  
Jianhao Liu ◽  
Tingyue Zheng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Tumor Cells ◽  
Crucial Role ◽  
Tumor Invasion ◽  
Cancer Associated Fibroblasts ◽  
Invasion And Metastasis ◽  
Promising Strategy

Cancer-associated fibroblasts (CAFs) play a crucial role in facilitating tumor invasion and metastasis, which act as the “soils” in tumor microenvironment (TME). Accordingly, it would be a promising strategy to...

scholarly journals Telomere length variation in tumor cells and cancer-associated fibroblasts: potential biomarker for hepatocellular carcinoma

2017 ◽  
Vol 243 (4) ◽  
pp. 407-417 ◽  
Author(s):  
Li-Jie Ma ◽  
Xiao-Ying Wang ◽  
Meng Duan ◽  
Long-Zi Liu ◽  
Jie-Yi Shi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Telomere Length ◽  
Tumor Cells ◽  
Length Variation ◽  
Cancer Associated Fibroblasts ◽  
Potential Biomarker
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