How does the tumor microenvironment play a role in hepatobiliary tumors?

Abstract

The tumor microenvironment (TME) is defined as the structural and dynamic network of cellular and non-cellular interactions between malignant cells and the surrounding non-malignant matrix. Hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC) are two of the most challenging gastrointestinal malignancies. Despite clinical advancements in understanding tumor biology and growth of the chemotherapeutic industry, there have been no corresponding improvements in prognosis and overall survival of HCC and PDAC. Both of these cancers have a very intimate relationship with their surrounding environment; the TME is thought to actively participate in initiating and sustaining these malignancies. Individual TME constituents play a vital role in chemoresistance and recurrence after surgery and have been established as independent prognostic factors. This review article will highlight the diverse structural components, key signaling pathways, and extracellular matrices of HCC and PDAC and discuss their crosstalk with tumor cells to promote growth and metastasis. The article will also summarize the latest laboratory and clinical research based on therapeutic targets identified within the TME of both HCC and PDAC.

Elevated N‐methyltransferase expression induced by hepatic stellate cells contributes to the metastasis of hepatocellular carcinoma via regulation of the CD44v3 isoform

“…Although the role of the tumor microenvironment in tumor progression is well established (Amicone and Marchetti, ; Kamil and Rowe, ), the cross‐talk between HSC and HCC cells in liver cancer metastasis has hardly been explored. Our previous study showed that activated HSCs create an immunosuppressive microenvironment in an orthotopic liver tumor mouse model by inducing expansion of the Tregs and MDSCs (Zhao et al , ) (Zhao et al , ).…”

Macrophage-derived extracellular vesicles: diverse mediators of pathology and therapeutics in multiple diseases

“…Throughout the tumor microenvironment (TME), multiple cell type such as immune cells, vascular endothelial cells, and fibroblasts collectively work to regulate tumorigenesis. Disorders of the TME increase the occurrence of tumor recurrence, metastasis, and chemoresistance 95 . TAMs are one of the major TME cells that provide an immunosuppressive milieu for tumor progression and secrete many growth factors that suppress the proinflammatory cytokine release in the TME.…”

Macrovascular Endothelial Cells Enhance the Motility of Liver Cancer Cells by Up-regulation of MMP-3, Activation of Integrin/FAK Signaling Pathway and Induction of Non-classical Epithelial-mesenchymal Transition

“…The hepatic stromal cells include vascular endothelial cells, sinusoidal endothelial cells, stellate cells, adipose cells, liver progenitor cells, immune inflammatory cells and cancer-associated fibroblasts. The crosstalk between liver cancer cells and immune inflammatory cells as well as cancer-associated fibroblasts significantly influences tumor growth and metastasis [6][7][8][9]. It has also been documented that higher levels of activated hepatic stellate cells are associated to the increased portal vein invasion by up-regulation of integrins/FAK signaling pathway and MMP levels [10].…”