A Starring Role for Stellate Cells in the Pancreatic Cancer Microenvironment

Abstract

Pancreatic ductal adenocarcinoma is a devastating disease, and patient outcomes have not improved in decades. Treatments that target tumor cells have largely failed. This could be because research has focused on cancer cells and the influence of the stroma on tumor progression has been largely ignored. The focus of pancreatic cancer research began to change with the identification of pancreatic stellate cells, which produce the pancreatic tumor stroma. There is compelling in vitro and in vivo evidence for the influence of pancreatic stellate cells on pancreatic cancer development; several recent preclinical studies have reported encouraging results with approaches designed to target pancreatic stellate cells and the stroma. We review the background and recent advances in these areas, along with important areas of future research that could improve therapy.

Adipose Triglyceride Lipase (ATGL) Expression Is Associated with Adiposity and Tumor Stromal Proliferation in Patients with Pancreatic Ductal Adenocarcinoma

“…Pancreatic stellate cells (PSCs) are resident cells of the pancreas, comprise approximately 5% of the pancreatic parenchyma (21) and have the important function of maintaining the balance of extracellular matrix synthesis and degradation (22). PSCs undergo a phenotypic transformation from a quiescent state to a myofibroblast-like state during times of pancreatic injury in response to stressors such as ethanol, oxidants and various cytokines (21)(22)(23)(24). The results of our study suggest that ATGL might mediate an increase in tumor stroma, possibly by increasing free fatty acid content in the tumor microenvironment, thereby contributing to the phenotypic change of PSCs into an extracellular matrixsecreting state.…”

Cholangiocarcinoma-derived exosomes inhibit the antitumor activity of cytokine-induced killer cells by down-regulating the secretion of tumor necrosis factor-α and perforin

“…The data above showed that TEX down-regulated the population of CD3 + , CD8 + , NK (CD56 + ), and CD3 + CD56 + cells, especially the population of CD3 + CD56 + cells, resulting in the secretion decreases of TNF-α and perforin, thus the antitumor ability of the TEX-CIK group was lower than that of the N-CIK group. An increasing number of literature show that transforming growth factor-β (TGF-β), Wnt signaling components, phosphatase and tensin homolog (PTEN), epidermal growth factor receptor (EGFR), and Fas ligand may play important roles in exosomemeditated tumor immunosuppression (Apte et al, 2013). Thus, the further mechanism underlying the depletion of CD3 + CD56 + CIK cells upon exosome treatment needs additional research.…”

150 MicroRNA-199a and 214 as potential therapeutic targets in pancreatic stellate cells in pancreatic tumor

“…Many studies have shown that the differentiated hPSCs elicit pro-tumorigenic effects by secreting growth factors and cytokines, and thereby induce tumor progression, invasion, and metastasis [11,17].…”

“…Pancreatic stellate cells (PSCs), the quiscent Vitamin A storing cells in pancreas, are the main precursor cells for CAFs [11]. During pancreatic injury or inflammation, PSCs are activated by pro-inflammatory cytokines and www.impactjournals.com/oncotarget various growth factors and differentiate into alphasmooth muscle actin (α-SMA)-expressing myofibroblasts [12][13][14][15].…”