Cancer-Associated Fibroblasts and Tumor Cells in Pancreatic Cancer Microenvironment and Metastasis: Paracrine Regulators, Reciprocation and Exosomes
Yoshiaki Sunami, Johanna Häußler, Anais Zourelidis, Jörg Kleeff
Abstract
Pancreatic cancer is currently the fourth leading cause of cancer deaths in the United States, and the overall 5 year survival rate is still only around 10%. Pancreatic cancer exhibits a remarkable resistance to established therapeutic options such as chemotherapy and radiotherapy, in part due to the dense stromal tumor microenvironment, where cancer-associated fibroblasts are the major stromal cell type. Cancer-associated fibroblasts further play a key role in cancer progression, invasion, and metastasis. Cancer-associated fibroblasts communicate with tumor cells, not only through paracrine as well as paracrine-reciprocal signaling regulators but also by way of exosomes. In the current manuscript, we discuss intercellular mediators between cancer-associated fibroblasts and pancreatic cancer cells in a paracrine as well as paracrine-reciprocal manner. Further recent findings on exosomes in pancreatic cancer and metastasis are summarized.