title: Pancreatic stellate cell: Pandora's box for pancreatic disease biology.
abstract: Pancreatic stellate cells (PSCs) were identified in the early 1980s, but received much attention after 1998 when the methods to isolate and culture them from murine and human sources were developed. PSCs contribute to a small proportion of all pancreatic cells under physiological condition, but are essential for maintaining the normal pancreatic architecture. Quiescent PSCs are characterized by the presence of vitamin A laden lipid droplets. Upon PSC activation, these perinuclear lipid droplets disappear from the cytosol, attain a myofibroblast like phenotype and expresses the activation marker, alpha smooth muscle actin. PSCs maintain their activated phenotypeviaan autocrine loop involving different cytokines and contribute to progressive fibrosis in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC). Several pathways (e.g., JAK-STAT, Smad, Wnt signaling, Hedgehogetc.), transcription factors and miRNAs have been implicated in the inflammatory and profibrogenic function of PSCs. The role of PSCs goes much beyond fibrosis/desmoplasia in PDAC. It is now shown that PSCs are involved in significant crosstalk between the pancreatic cancer cells and the cancer stroma. These interactions result in tumour progression, metastasis, tumour hypoxia, immune evasion and drug resistance. This is the rationale for therapeutic preclinical and clinical trials that have targeted PSCs and the cancer stroma.
authors.affiliation: Ratnakar R Bynigeri, Aparna Jakkampudi, Ramaiah Jangala, Chivukula Subramanyam, Mitnala Sasikala, G Venkat Rao, D Nageshwar Reddy, Rupjyoti Talukdar, Institute of Basic Sciences, Asian Healthcare Foundation, Hyderabad 500082, India.
authors.forename: Ratnakar R
authors.initials: RR
authors.lastname: Bynigeri
authors.affiliation: Ratnakar R Bynigeri, Aparna Jakkampudi, Ramaiah Jangala, Chivukula Subramanyam, Mitnala Sasikala, G Venkat Rao, D Nageshwar Reddy, Rupjyoti Talukdar, Institute of Basic Sciences, Asian Healthcare Foundation, Hyderabad 500082, India.
authors.forename: Aparna
authors.initials: A
authors.lastname: Jakkampudi
authors.affiliation: Ratnakar R Bynigeri, Aparna Jakkampudi, Ramaiah Jangala, Chivukula Subramanyam, Mitnala Sasikala, G Venkat Rao, D Nageshwar Reddy, Rupjyoti Talukdar, Institute of Basic Sciences, Asian Healthcare Foundation, Hyderabad 500082, India.
authors.forename: Ramaiah
authors.initials: R
authors.lastname: Jangala
authors.affiliation: Ratnakar R Bynigeri, Aparna Jakkampudi, Ramaiah Jangala, Chivukula Subramanyam, Mitnala Sasikala, G Venkat Rao, D Nageshwar Reddy, Rupjyoti Talukdar, Institute of Basic Sciences, Asian Healthcare Foundation, Hyderabad 500082, India.
authors.forename: Chivukula
authors.initials: C
authors.lastname: Subramanyam
authors.affiliation: Ratnakar R Bynigeri, Aparna Jakkampudi, Ramaiah Jangala, Chivukula Subramanyam, Mitnala Sasikala, G Venkat Rao, D Nageshwar Reddy, Rupjyoti Talukdar, Institute of Basic Sciences, Asian Healthcare Foundation, Hyderabad 500082, India.
authors.forename: Mitnala
authors.initials: M
authors.lastname: Sasikala
authors.affiliation: Ratnakar R Bynigeri, Aparna Jakkampudi, Ramaiah Jangala, Chivukula Subramanyam, Mitnala Sasikala, G Venkat Rao, D Nageshwar Reddy, Rupjyoti Talukdar, Institute of Basic Sciences, Asian Healthcare Foundation, Hyderabad 500082, India.
authors.forename: G Venkat
authors.initials: GV
authors.lastname: Rao
authors.affiliation: Ratnakar R Bynigeri, Aparna Jakkampudi, Ramaiah Jangala, Chivukula Subramanyam, Mitnala Sasikala, G Venkat Rao, D Nageshwar Reddy, Rupjyoti Talukdar, Institute of Basic Sciences, Asian Healthcare Foundation, Hyderabad 500082, India.
authors.forename: D Nageshwar
authors.initials: DN
authors.lastname: Reddy
authors.affiliation: Ratnakar R Bynigeri, Aparna Jakkampudi, Ramaiah Jangala, Chivukula Subramanyam, Mitnala Sasikala, G Venkat Rao, D Nageshwar Reddy, Rupjyoti Talukdar, Institute of Basic Sciences, Asian Healthcare Foundation, Hyderabad 500082, India.
authors.forename: Rupjyoti
authors.initials: R
authors.lastname: Talukdar
mesh_terms: D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D016207:Cytokines / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D009361:Neoplasm Invasiveness; D046790:Pancreas, Exocrine / Q000166:cytology / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D058954:Pancreatic Stellate Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D050500:Pancreatitis, Chronic / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D015398:Signal Transduction; D059016:Tumor Microenvironment
chemical_list: D016207:Cytokines; D016326:Extracellular Matrix Proteins; D035683:MicroRNAs
keywords: Pancreatic cancer stroma; Pancreatic fibrosis; Pancreatic stellate cells; Pancreatic stellate cells-cancer-stromal interactions; Physiological functions; Therapeutic targets