Alteration of pancreatic cancer cell functions by tumor-stromal cell interaction

• Main Authors: Shin eHamada, Atsushi eMasamune, Tooru eShimosegawa
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2013-11-01
• Series: Frontiers in Physiology
• Subjects: Epithelial-Mesenchymal Transition; Mast Cells; Pancreatic Stellate Cells; cancer stem cells; desmoplasia; bone marrow derived cells
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fphys.2013.00318/full

Pancreatic cancer shows a characteristic tissue structure called desmoplasia, which consists of dense fibrotic stroma surrounding cancer cells. Interactions between pancreatic cancer cells and stromal cells promote invasive growth of cancer cells and establish a specific microenvironment such as hypoxia which further aggravates the malignant behavior of cancer cells. Pancreatic stellate cells (PSCs) play pivotal role in the development of fibrosis within the pancreatic cancer tissue, and also affect the cancer cell functions. PSCs induce epithelial-mesenchymal transition and cancer stem cell (CSC)-related phenotypes in pancreatic cancer cells by activating multiple signaling pathways. In addition, pancreatic cancer cells and PSCs recruit myeloid-derived suppressor cells which attenuate the immune reaction against pancreatic cancer cells. As a result, pancreatic cancer cells become refractory against conventional therapies. The formation of the CSC-niche by stromal cells facilitates postoperative recurrence, re-growth of therapy-resistant tumors and distant metastasis. Conventional therapies targeting cancer cells failed to conquer pancreatic cancer, but targeting stromal cells and immune cells effectively improved the therapeutic responses in experimental conditions. A combination of novel strategies altering stromal cell functions could contribute to improving the pancreatic cancer prognosis.