Article Commentary: TGF-β Mediated Crosstalk between Malignant Hepatocyte and Tumor Microenvironment in Hepatocellular Carcinoma

Abstract

In this article, we have reviewed current literature regarding the regulation of hepatocellular carcinoma (HCC) by the interaction of malignant hepatocytes and their tissue environment through cytokine signaling, here represented by transforming growth factor-beta (TGF-β) signaling. We have discussed responses of TGF-β signaling in transition of hepatic stellate cells to myofibroblasts (MFBs), recruitment of tumor-associated macrophages (TAMs), and enrichment of tumor-associated endothelial cells (TECs). The malignant hepatocytes also secrete various factors such as platelet-derived growth factors (PDGFs), vascular endothelial growth factor (VEGF), and TGF-β. TGF-β, a super-family of cytokines, creates tumor microenvironment by interacting through other growth factors (epidermal growth factor receptor (EGFR), PDGF, fibroblast growth factor (FGF), hepatocyte growth factor (HGF), VEGF), cytokines and chemokines, and extracellular matrix (ECM) remodeling. Hence, the HCC tumor microenvironment may now be recognized as an important participant of tumor progression to act as potential target to systemic therapies compared to targeted therapies.

RETRACTED ARTICLE: TGF-β secreted by tumor-associated macrophages promotes proliferation and invasion of colorectal cancer via miR-34a-VEGF axis

“…TAMs can affect tumor invasion and metastasis ability by secreting various cytokines, and is closely associated with tumor cell proliferation and apoptosis. Recent studies have highlighted that TGF-β signal transduction pathway is considered to be involved in the crosstalk between TAMs and tumor cells in tumor microenvironment [7]. There is increasing evidence emerging to suggest that TGF-β plays crucial roles in pathophysiological processes by regulating multiple microRNAs (miRNAs).…”

New Mechanisms of Tumor-Associated Macrophages on Promoting Tumor Progression: Recent Research Advances and Potential Targets for Tumor Immunotherapy

“…EMT is considered the key step via which tumor cells gain the greater capacity for invasiveness and metastasis. TAMs can strongly express many kinds of cytokines that can induce EMT, such as TGF- β and IL-6 [73]. TNF- α secreted by TAMs has been shown to activate NF- κ B-mediated transcription of Snail1 and Zeb, which leads to diminished E-cadherin expression on tumor cells [74].…”

Tumor-stroma ratio (TSR) in non-small cell lung cancer (NSCLC) patients after lung resection is a prognostic factor for survival

“…(23). Transforming growth factor-β plays a vital part in the evolution of the tumor microenvironment (24).…”