Interplay between Cellular and Non-Cellular Components of the Tumour Microenvironment in Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide. Currently, treatments available for advanced HCC provide dismal chances of survival, thus there is an urgent need to develop more effective therapeutic strategies. While much of the focus of recent decades has been on targeting malignant cells, promising results have emerged from targeting the tumour microenvironment (TME). The extracellular matrix (ECM) is the main non-cellular component of the TME and it profoundly changes during tumorigenesis to promote the growth and survival of malignant cells. Despite this, many in vitro models for drug testing fail to consider the TME leading to a high failure rate in clinical trials. Here, we present an overview of the function and properties of the ECM in the liver and how these change during malignant transformation. We also discuss the relationship between immune cells and ECM in the TME in HCC. Lastly, we present advanced, 3D culture techniques of cancer modelling and argue that the incorporation of TME components into these is essential to better recapitulate the complex interactions within the TME.

Tumor-Derived Extracellular Vesicles Regulate Cancer Progression in the Tumor Microenvironment

“…The ECM is a highly dynamic three-dimensional network composed of plenty of fibrous proteins and glycoproteins ( Mouw et al, 2014 ). Tumors often exhibit ECM deposition and degradation, and this dysregulation state supports tumorigenesis and metastasis and induces angiogenesis ( Sükei et al, 2021 ). Cytokines are small molecular polypeptides or proteins that serve as immunomodulatory effectors.…”

Change of tumor-infiltrating lymphocyte of associating liver partition and portal vein ligation for staged hepatectomy for hepatocellular carcinoma

“…In the past few decades, researchers have gained a deeper understanding of the importance of the TME in the occurrence, development, invasion, and metastasis of HCC[ 26 ]. The dynamic changes of the TME significantly affect the tumor biological characteristics of HCC.…”

Drug Metabolism for the Identification of Clinical Biomarkers in Breast Cancer

“…Furthermore, the relationship between cellular and non-cellular components must be acknowledged since they are vital regulators of primary tumor progression, organ-specific metastasis, and therapeutic response. The extracellular matrix (ECM) is the main non-cellular component of the TME, and it undergoes significant changes during tumorigenesis to aid malignant cell growth and survival [ 22 ]. Large ECM deposits in solid tumors can account for up to 60% of the tumor’s bulk.…”

“…Proteases cause the release of cytokines and growth factors that are stored in the ECM [ 23 ]. Proangiogenic factors, including VEGF, FGF, PDGFB, and TGFB, can be found in the ECM [ 22 ].…”

“…It can be utilized to control tumor cells, affecting tumor start, development, and advancement in a variety of ways. TME cells and chemicals can boost tumor cell stemness, stimulate angiogenesis, mediate migration, cause treatment resistance, and inhibit the immune system [ 22 ]. Taking all of this into account, the immunological TME evaluation has crucial predictive value and can enhance histopathological and molecular indicators in evaluating patient responses to treatment.…”