Pancreatic Stellate Cells: Partners in Crime with Pancreatic Cancer Cells
Alain Vonlaufen,Swapna Joshi,Changfa Qu,Phoebe A. Phillips,Zhihong Xu,Nicole R. Parker,Cheryl S. Toi,Romano C. Pirola,Jeremy S. Wilson,David Goldstein,Minoti V. Apte +10 more
TLDR
A significant interaction between pancreatic cancer cells and stromal cells (PSCs) is indicated and imply that pancreaticcancer cells recruit stronal cells to establish an environment that promotes cancer progression.Abstract:
Pancreatic stellate cells (PSC) produce the stromal reaction in pancreatic cancer, but their role in cancer progression is not fully elucidated. We examined the influence of PSCs on pancreatic cancer growth using (a) an orthotopic model of pancreatic cancer and (b) cultured human PSCs (hPSC) and human pancreatic cancer cell lines MiaPaCa-2 and Panc-1. Athymic mice received an intrapancreatic injection of saline, hPSCs, MiaPaCa-2 cells, or hPSCs + MiaPaCa-2. After 7 weeks, tumor size, metastases, and tumor histology were assessed. In vitro studies assessed the effect of cancer cell secretions on PSC migration and the effect of hPSC secretions on cancer cell proliferation, apoptosis, and migration. Possible mediators of the effects of hPSC secretions on cancer cell proliferation were examined using neutralizing antibodies. Compared with mice receiving MiaPaCa-2 cells alone, mice injected with hPSCs + MiaPaCa-2 exhibited (a) increased tumor size and regional and distant metastasis, (b) fibrotic bands (desmoplasia) containing activated PSCs within tumors, and (c) increased tumor cell numbers. In vitro studies showed that, in the presence of pancreatic cancer cells, PSC migration was significantly increased. Furthermore, hPSC secretions induced the proliferation and migration, but inhibited the apoptosis, of MiaPaCa-2 and Panc-1 cells. The proliferative effect of hPSC secretions on pancreatic cancer cells was inhibited in the presence of neutralizing antibody to platelet-derived growth factor. Our studies indicate a significant interaction between pancreatic cancer cells and stromal cells (PSCs) and imply that pancreatic cancer cells recruit stromal cells to establish an environment that promotes cancer progression.read more
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Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma
Richard A. Moffitt,Raoud Marayati,Elizabeth L. Flate,Keith E. Volmar,S. Gabriela Herrera Loeza,Katherine A. Hoadley,Naim U. Rashid,Lindsay A. Williams,Samuel C. Eaton,Alexander H. Chung,Jadwiga K. Smyla,Judy M. Anderson,Hong Jin Kim,David J. Bentrem,Mark S. Talamonti,Christine A. Iacobuzio-Donahue,Michael A. Hollingsworth,Jen Jen Yeh +17 more
TL;DR: By digitally separating tumor, stromal and normal gene expression, two tumor subtypes are identified and validated, including a 'basal-like' subtype that has worse outcome and is molecularly similar to basal tumors in bladder and breast cancers.
Journal ArticleDOI
The Pancreas Cancer Microenvironment
Christine Feig,Aarthi Gopinathan,Albrecht Neesse,Derek S. Chan,Natalie Cook,David A. Tuveson +5 more
TL;DR: The current understanding of the PDA tumor microenvironment is reviewed, opportunities for further exploration that may benefit patients are highlighted, and methods that alter stromal composition or function are under active investigation.
Journal ArticleDOI
Vitamin D Receptor-Mediated Stromal Reprogramming Suppresses Pancreatitis and Enhances Pancreatic Cancer Therapy
Mara H. Sherman,Ruth T. Yu,Dannielle D. Engle,Ning Ding,Annette R. Atkins,Hervé Tiriac,Eric A. Collisson,Frances Connor,Terry Van Dyke,Serguei Kozlov,Philip Martin,Tiffany W. Tseng,David W. Dawson,Timothy R. Donahue,Atsushi Masamune,Tooru Shimosegawa,Minoti V. Apte,Jeremy S. Wilson,Beverly Ng,Beverly Ng,Sue Lynn Lau,Sue Lynn Lau,Sue Lynn Lau,Jenny E. Gunton,Geoffrey M. Wahl,Tony Hunter,Jeffrey A. Drebin,Peter J. O'Dwyer,Christopher Liddle,David A. Tuveson,Michael Downes,Ronald M. Evans,Ronald M. Evans +32 more
TL;DR: It is shown that VDR acts as a master transcriptional regulator of PSCs to reprise the quiescent state, resulting in induced stromal remodeling, increased intratumoral gemcitabine, reduced tumor volume, and a 57% increase in survival compared to chemotherapy alone.
Journal ArticleDOI
Stromal biology and therapy in pancreatic cancer
Albrecht Neesse,Patrick Michl,Kristopher K. Frese,Christine Feig,Natalie Cook,Mike A Jacobetz,Martijn P. Lolkema,Malte Buchholz,Kenneth P. Olive,Thomas M. Gress,David A. Tuveson +10 more
TL;DR: Stromal cells contained within the PDA tumour microenvironment represent an additional constituent to neoplastic cells that should be critically evaluated for optimal therapeutic development in preclinical models and early clinical trials.
Journal ArticleDOI
KRAS, Hedgehog, Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma.
TL;DR: This work examines the central part that KRAS plays in the biology of PDAC, and how the timing and location of Hh and Wnt–β-catenin signalling dictate the specification and oncogenic properties ofPDAC.
References
More filters
Journal ArticleDOI
Cancer statistics, 2006.
Ahmedin Jemal,Rebecca L. Siegel,Elizabeth Ward,Taylor Murray,Jiaquan Xu,Carol Smigal,Michael J. Thun +6 more
TL;DR: The American Cancer Society estimated the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute and mortality data from National Center for Health Statistics as discussed by the authors.
Journal ArticleDOI
Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium.
Aria F. Olumi,Gary D. Grossfeld,Simon W. Hayward,Peter R. Carroll,Thea D. Tlsty,Gerald R. Cunha +5 more
TL;DR: In this paper, the authors demonstrate that fibroblasts associated with carcinomas stimulate tumor progression of initiated nontumorigenic epithelial cells both in an in vivo tissue recombination system and in vitro coculture system.
Book
Histological and Histochemical Methods: Theory and Practice
TL;DR: This text presents the chemical and physical principles of fixation, staining and histochemistry, and offers a practical guide to the preparation of specimens for light microscopy and includes detailed practical instructions of the techniques used.
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