The impact of cancer-associated fibroblasts on major hallmarks of pancreatic cancer

Abstract

Pancreatic ductal adenocarcinoma (PDAC) constitutes one of the most challenging lethal tumors and has a very poor prognosis. In addition to cancer cells, the tumor microenvironment created by a repertoire of resident and recruited cells and the extracellular matrix also contribute to the acquisition of hallmarks of cancer. Among these factors, cancer-associated fibroblasts (CAFs) are critical components of the tumor microenvironment. CAFs originate from the activation of resident fibroblasts and pancreatic stellate cells, the differentiation of bone marrow-derived mesenchymal stem cells and epithelial-to-mesenchymal transition. CAFs acquire an activated phenotype via various cytokines and promote tumor proliferation and growth, accelerate invasion and metastasis, induce angiogenesis, promote inflammation and immune destruction, regulate tumor metabolism, and induce chemoresistance; these factors contribute to the acquisition of major hallmarks of PDAC. Therefore, an improved understanding of the impact of CAFs on the major hallmarks of PDAC will highlight the diagnostic and therapeutic values of these targeted cells.

GATA3 suppresses human fibroblasts-induced metastasis of clear cell renal cell carcinoma via an anti-IL6/STAT3 mechanism

“…Tumor metastasis is usually associated with abnormal expression of cytokines, especially CXCL12 [42][43][44][45][46], VEGF [47,48], IL1β [49,50], and IL6 [51,52], while CAFs can promote tumor growth and invasion via a plethora of active factors [53]. We therefore checked these specific cytokines in different cancer cells with the presence or absence of different NF-CMs.…”

“…GATA3 has been reported as a sensitive and specific marker for urothelial and breast carcinomas in tissue sections [53]. However, it may have differential impacts on different organs [57].…”

Ping-Pong—Tumor and Host in Pancreatic Cancer Progression

“…The DR provides a barrier for immune cells, but also for chemotherapy by poor drug access (481). Beyond this "passive action, " aPSC/CAF contribute to the acquisition of major hallmarks of PaCa via cytokines, chemokines, growth factors, and their receptors that promote tumor cell proliferation and chemoresistance, accelerate intrapancreatic nerve invasion and distant metastatic growth and assist establishing an inflammatory milieu that forces immune destruction (482). aPSC/CAF supply essential nutrients and promote metabolic reprogramming backing tumor cell survival and proliferation (483), which is assisted by aPSC/CAF miRNA (484).…”

Evaluation of Cancer-Associated Fibroblasts Markers in Hepatocellular Carcinoma

“…An interaction between tumor cells and stroma forms what is known as tumorhost microenvironment [3] . Tumor microenviroment acts a pivotal role in tumor growth and progression, metastasis , in angiogensis and resistance to chemotherapy [4] .…”