The extracellular matrix in hepatocellular carcinoma: Mechanisms and therapeutic vulnerability

Roy, Arya Mariam; Iyer, Renuka; Chakraborty, Sayan

doi:10.1016/j.xcrm.2023.101170

Cited by 17 publications

(10 citation statements)

References 148 publications

(180 reference statements)

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“…Disorganized ECM contributes to the formation of the tumor microenvironment. Excessive ECM deposition in the liver could lead to liver fibrosis and cirrhosis, which predispose to HCC and promote tumor growth and metastasis by inducing inflammatory factors, promoting abnormal vasculature, and increasing tissue rigidity [35]. In the current study, the PH-treated kras+ zebrafish livers have shown enhanced ECM gene expressions, which could contribute to the speed of tumorigenesis.…”

Section: Discussionmentioning

confidence: 60%

“…Consistent with the enhanced cell proliferation, the liver expression of cell cycle-related genes, including ccnb1 and cdk1, was promoted significantly by PH (Figure 2C). Extracellular matrix (ECM) accumulation in the liver can contribute to tumor metastasis during HCC development [35]. In our experiments, the expression of genes encoding ECM, including col1a1b and lama5, was significantly increased by PH in the kras+ livers (Figure 2D).…”

Section: Ph Enhanced the Hcc-associated Features In Kras+ Zebrafishmentioning

confidence: 65%

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Partial Hepatectomy Promotes the Development of KRASG12V-Induced Hepatocellular Carcinoma in Zebrafish

Zhu,

Li,

Liu

et al. 2024

Cancers

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The purpose of this study was to investigate the effects of PH on the development of oncogenic krasG12V-induced HCC in zebrafish. The inducible HCC model in Tg(fabp10a:rtTA2s-M2; TRE2:EGFP-krasG12V) zebrafish was used. PH or sham surgery was performed before the induction of oncogenic krasG12V expression in the livers of transgenic zebrafish. Histological analysis was carried out to determine the progression of HCC and other HCC-associated features including hepatocyte proliferation, extracellular matrix production, and local oxidative stress. The similarity between the process of PH-induced liver regeneration and that of krasG12V-induced HCC development was further compared by RNA-Seq analysis. The results show that PH promotes the development of krasG12V-induced HCC in zebrafish possibly through enhancing neutrophil-mediated oxidative stress and promoting the upregulation of s100a1, and the downregulation of ribosome biogenesis.

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Section: Discussionmentioning

confidence: 60%

Section: Ph Enhanced the Hcc-associated Features In Kras+ Zebrafishmentioning

confidence: 65%

Partial Hepatectomy Promotes the Development of KRASG12V-Induced Hepatocellular Carcinoma in Zebrafish

Zhu,

Li,

Liu

et al. 2024

Cancers

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“…Within the hepatocellular carcinoma (HCC) microenvironment, the extracellular matrix (ECM) assumes a pivotal role, providing structural integrity to the tumor and orchestrating cellular behavior through signaling molecules such as growth factors and cytokines. Alterations in ECM composition and stiffness can profoundly impact tumor dynamics, fostering growth, invasion, and metastasis [32,33].…”

Section: Hepatocellular Carcinoma and The Tumor Microenvironmentmentioning

confidence: 99%

Hepatocellular Carcinoma and the Multifaceted Relationship with Its Microenvironment: Attacking the Hepatocellular Carcinoma Defensive Fortress

Galasso,

Cerrito,

Maccauro

et al. 2024

Cancers

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Hepatocellular carcinoma is a malignant tumor that originates from hepatocytes in an inflammatory substrate due to different degrees of liver fibrosis up to cirrhosis. In recent years, there has been growing interest in the role played by the complex interrelationship between hepatocellular carcinoma and its microenvironment, capable of influencing tumourigenesis, neoplastic growth, and its progression or even inhibition. The microenvironment is made up of an intricate network of mesenchymal cells, immune system cells, extracellular matrix, and growth factors, as well as proinflammatory cytokines and translocated bacterial products coming from the intestinal microenvironment via the enterohepatic circulation. The aim of this paper is to review the role of the HCC microenvironment and describe the possible implications in the choice of the most appropriate therapeutic scheme in the prediction of tumor response or resistance to currently applied treatments and in the possible development of future therapeutic perspectives, in order to circumvent resistance and break down the tumor’s defensive fort.

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“…), and increased expression of coinhibitory lymphocyte signals, including immune checkpoint ligands and receptors, collectively establish an immunosuppressive microenvironment in the context of liver cancer 39 . Collagen is the predominant protein found in the HCC microenvironment and plays a critical role in the structure of the tumor microenvironment 40 (Figure 2). It is capable of modulating the immune microenvironment through a series of ligand–receptor inteactions, resembling a “lock and key” mechanism 41–44 .…”

Section: The Role and Modification Of Collagen In Hccmentioning

confidence: 99%

“…The collagen-rich HCC microenvironment also leads to enhanced mechanotransduction 40 . In the HCC microenvironment, cells are exposed to a variety of physical forces, including tensile, compressive, shear, and static mechanical forces, where cells convert mechanical stimuli into biochemical signals that lead to changes in cellular behavior 50 .…”

Section: The Role and Modification Of Collagen In Hccmentioning

confidence: 99%

Collagen in hepatocellular carcinoma: A novel biomarker and therapeutic target

Ding,

Jiang,

et al. 2024

Hepatology Communications

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HCC is globally recognized as a major health threat. Despite significant progress in the development of treatment strategies for liver cancer, recurrence, metastasis, and drug resistance remain key factors leading to a poor prognosis for the majority of liver cancer patients. Thus, there is an urgent need to develop effective biomarkers and therapeutic targets for HCC. Collagen, the most abundant and diverse protein in the tumor microenvironment, is highly expressed in various solid tumors and plays a crucial role in the initiation and progression of tumors. Recent studies have shown that abnormal expression of collagen in the tumor microenvironment is closely related to the occurrence, development, invasion, metastasis, drug resistance, and treatment of liver cancer, making it a potential therapeutic target and a possible diagnostic and prognostic biomarker for HCC. This article provides a comprehensive review of the structure, classification, and origin of collagen, as well as its role in the progression and treatment of HCC and its potential clinical value, offering new insights into the diagnosis, treatment, and prognosis assessment of liver cancer.

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The extracellular matrix in hepatocellular carcinoma: Mechanisms and therapeutic vulnerability

Cited by 17 publications

References 148 publications

Partial Hepatectomy Promotes the Development of KRASG12V-Induced Hepatocellular Carcinoma in Zebrafish

Partial Hepatectomy Promotes the Development of KRASG12V-Induced Hepatocellular Carcinoma in Zebrafish

Hepatocellular Carcinoma and the Multifaceted Relationship with Its Microenvironment: Attacking the Hepatocellular Carcinoma Defensive Fortress

Collagen in hepatocellular carcinoma: A novel biomarker and therapeutic target

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