Pancreatic adenocarcinoma is a highly lethal disease that is histologically characterized by a dense desmoplastic reaction (DR) surrounding malignant epithelial cells. The DR is composed of extracellular matrix (ECM) proteins, fibroblasts, stellate cells, endothelial cells, immune cells, and neurons. Accumulating evidence indicates that the epithelial and stromal compartments interact to enhance the aggressive nature of this disease. Pancreatic cancer cells release various factors that stimulate the stroma. Stromal cells, in turn, release mitogenic substances that stimulate tumor growth, invasion, and resistance to therapy. As we better understand the interactions between the stromal and epithelial cell compartments in pancreatic adenocarcinoma, it is becoming evident that anticancer therapies targeting the stroma, in addition to epithelial cells, may play a key role in improving clinical outcomes for patients with this deadly disease.

Contents

• Preface
  Paul Grippo, PhD and Hidayatullah G. Munshi, MD.
• Foreward: It takes two to tango : Pancreatic cancer and its microenvironment
  Minoti Apte, MBBS., MMedSci., PhD., AGAF.
• Contributors
• 1. Pathology of pancreatic stroma in PDAC
  Zeshaan A. Rasheed, William Matsui, and Anirban Maitra.
  • Introduction
  • Pancreatic cancer stellate cells and fibroblasts
  • Endothelial cells
  • Inflammatory cells
  • Pericytes and nerve cells
  • Clinically targeting the pancreatic stroma
  • References
• 2. Imaging the pancreatic ECM
  Palamadai N. Venkatasubramanian.
  • Introduction
  • ECM composition
  • Function of stroma in health and pathology
  • ECM in pancreatic cancer
  • Imaging the ECM
  • Summary and conclusions
  • References
• 3. Pancreatic stellate cells and fibrosis
  Phoebe Phillips.
  • Introduction
  • The microenvironment of pancreatic cancer
  • The biology of pancreatic stellate cells
  • Role of pancreatic stellate cells in pancreatic fibrosis
  • The role of cancer-stellate cell interactions in tumor progression
  • The hypoxia fibrosis cycle
  • Role of pancreatic stellate cells and fibrosis in epithelial- mesenchymal transition
  • Targeting pancreatic stellate cell mediated fibrosis: A potential therapy
  • Summary Points
  • Conclusion
  • Acknowledgements
  • References
• 4. Pancreatic cancer and the tumor microenvironment: Mesenchyme’s role in pancreatic carcinogenesis
  Laurent Bartholin.
  • Introduction
  • I. Different types of mouse models of pancreatic cancers
  • II. Contribution of mouse models in the understanding of pancreatic cancer cell-stroma interactions
  • IV. The TGFβ pathway
  • Conclusion-perspectives
  • References
• 5. Epithelial-mesenchymal transition and pancreatic cancer progression
  Surabhi Dangi-Garimella, Seth B. Krantz, Mario A. Shields, Paul J. Grippo, and Hidayatullah G. Munshi.
  • 1. Introduction
  • 2. Epithelial-mesenchymal transition and PDAC
  • 3. Role of microRNAs in modulating EMT in pancreatic cancer
  • 4. Contribution of EMT to stem cells in pancreatic cancer
  • 5. Importance of EMT in enhancing drug resistance in pancreatic cancer
  • 6. Targeting EMT in pancreatic cancer
  • Acknowledgements
  • References
• 6. Pancreatic cancer stem cell and mesenchymal stem cell
  Shin Hamada and Tooru Shimosegawa.
  • Introduction
  • Normal pancreatic stem cell and pancreatic CSC
  • Marker of normal pancreatic stem cell and CSC
  • Pancreatic cancer stem cell and therapy-resistance
  • Interaction of cancer cells and stromal cells
  • Role of MSC in pancreatic cancer
  • Microenvironment of pancreatic cancer; Role of hypoxia
  • Pancreatic cancer stromal cells as a possible CSC niche
  • Closing remarks
  • References
• 7. Signaling pathways mediating epithelial- mesenchymal crosstalk in pancreatic cancer: Hedgehog, Notch and TGFβ
  Jennifer M. Bailey and Steven D. Leach.
  • Introduction
  • Pancreatic stellate cells promote tumor progression
  • Epithelial-mesenchymal crosstalk: Focus on Hedgehog, Notch and TGFβ
  • Conclusion
  • References
• 8. Desmoplasia and chemoresistance in pancreatic cancer
  Clifford J. Whatcott, Richard G. Posner, Daniel D. Von Hoff, and Haiyong Han.
  • Introduction
  • Desmoplasia
  • Cellular components
  • Tumor-associated macrophages
  • Neutrophils and regulatory T cells
  • Non-cellular components
  • Desmoplasia induced chemoresistance
  • Biological chemoresistance
  • Physiological chemoresistance
  • Potential therapeutic approaches for reducing desmoplasia induced chemoresistance
  • Conclusions
  • Acknowledgements
  • References
• 9. Therapeutic targeting of pancreatic stroma
  Andrew S. Liss and Sarah P. Thayer.
  • Introduction
  • Targeting the stroma to enhance conventional chemotherapuetics
  • Extracellular matrix
  • Targeting the tumor vasculature
  • Conclusion
  • References