Human Pancreatic Cancer-Associated Stellate Cells Remain Activated after in vivo Chemoradiation.
Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extensive fibrotic reaction or desmoplasia and complex involvement of the surrounding tumor microenvironment. Pancreatic stellate cells are a key mediator of the pancreatic matrix and they promote progression and invasion of pancreatic cancer by increasing cell proliferation and offering protection against therapeutic interventions. Our study utilizes human tumor-derived pancreatic stellate cells (HTPSCs) isolated from fine needle aspirates of pancreatic cancer tissue from patients with locally advanced, unresectable pancreatic adenocarcinoma before and after treatment with full-dose gemcitabine plus concurrent hypo-fractionated stereotactic radiosurgery. We show that HTPSCs survive in vivo chemotherapy and radiotherapy treatment and display a more activated phenotype post-therapy. These data support the idea that stellate cells play an essential role in supporting and promoting pancreatic cancer and further research is needed to develop novel treatments targeting the pancreatic tumor microenvironment.
National Cancer Informatics Program, National Cancer Institute, National Institutes of Health , Bethesda, MD , USA ; Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University , Washington, DC , USA.
M Carla
MC
Cabrera
Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University , Washington, DC , USA.
Estifanos
E
Tilahun
Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University , Washington, DC , USA.
Rebecca
R
Nakles
Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University , Washington, DC , USA ; Department of Pharmaceutical Sciences, College of Pharmacy, Belmont University , Nashville, TN , USA.
Edgar S
ES
Diaz-Cruz
Department of Gastroenterology, Georgetown University , Washington, DC , USA.
Aline
A
Charabaty
Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University , Washington, DC , USA ; Department of Radiation Medicine, Georgetown University , Washington, DC , USA.
Simeng
S
Suy
Department of Surgery, Georgetown University , Washington, DC , USA.
Patrick
P
Jackson
Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University , Washington, DC , USA.
Lisa
L
Ley
Department of Biostatistics, University of Texas MD Anderson Cancer Center , Houston, TX , USA.
Rebecca
R
Slack
Department of Radiology, Georgetown University , Washington, DC , USA.
Reena
R
Jha
Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University , Washington, DC , USA ; Department of Radiation Medicine, Georgetown University , Washington, DC , USA.
Sean P
SP
Collins
Department of Gastroenterology, Georgetown University , Washington, DC , USA.
Nadim
N
Haddad
Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University , Washington, DC , USA ; Department of Pathology, Georgetown University , Washington, DC , USA.
Bhaskar V S
BV
Kallakury
Helmholtz Zentrum München - German Research Center for Environmental Health, Research Unit Stem Cell Dynamics , Neuherberg , Germany ; Department of Biosystems Science and Engineering, ETH Zurich , Basel , Switzerland.
Timm
T
Schroeder
Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University , Washington, DC , USA ; Department of Gastroenterology, Georgetown University , Washington, DC , USA ; Division of Hematology/Oncology, Department of Medicine, Georgetown University , Washington, DC , USA.
Michael J
MJ
Pishvaian
Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University , Washington, DC , USA ; Division of Hematology/Oncology, Department of Medicine, Georgetown University , Washington, DC , USA.
Priscilla A
PA
Furth
PDAC; chemotherapy; gemcitabine; pancreatic cancer; radiation; stellate cells