The dynamic interactions between the stroma,pancreatic stellate cells and pancreatic tumor development: Novel therapeutic targets |
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| Institution: | 1. Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia;2. Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia;3. Division of Gastroenterology, Tohoku University of Graduate School of Medicine, Sendai, Miyagi Prefecture 980–8574, Japan;4. University of Malaya Cancer Research Institute, University of Malaya, Kuala Lumpur 50603, Malaysia |
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| Abstract: | The stroma is a main driver of metastasis and aggressiveness in pancreatic cancer (PC), one of the deadliest malignancies worldwide. Pancreatic stellate cells (PSCs) form approximately 50% of the pancreatic tumor stroma, causing desmoplasia, extracellular matrix (ECM) deposition, epithelial-to-mesenchymal transition (EMT) and metastatic spread. Furthermore, activated PSCs can remodel the pancreatic tumor microenvironment (TME) via dynamic and complex interactions and feedback loops with PC cells, thus facilitating tumor growth through various signalling and immune pathways. Hence, increased understanding of these cellular cross-talks and how they shape the TME in PC might guide the development of novel treatment approaches against this stubborn and deadly malignancy that has so far resisted therapeutic advances. In this review, we will explore the role of the stroma and PSCs in PC development, invasion and metastasis, examine their interaction with PC cells and discuss potential treatment approaches aimed at targeting PSCs in order to reprogram the pancreatic tumor environment. |
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| Keywords: | Pancreatic stellate cells Tumor microenvironment Stroma Pancreatic cancer Targeted therapy Immunotherapy |
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