John A G Moir1, Jelena Mann2, Steve A White3. 1. Freeman Hospital, Department of HPB and Transplant Surgery, Newcastle upon Tyne, United Kingdom; Institute of Cellular Medicine, Fibrosis Lab, Newcastle upon Tyne, United Kingdom. Electronic address: drjagmoir@doctors.org.uk. 2. Institute of Cellular Medicine, Fibrosis Lab, Newcastle upon Tyne, United Kingdom. 3. Freeman Hospital, Department of HPB and Transplant Surgery, Newcastle upon Tyne, United Kingdom.
Abstract
BACKGROUND: The prognosis of pancreatic cancer remains desperately poor, with little progress made over the past 30 years despite the development of new combination chemotherapy regimens. Stromal activity is especially prominent in the tissue surrounding pancreatic tumours, and has a profound influence in dictating tumour development and dissemination. Pancreatic stellate cells (PaSCs) have a key role in this tumour microenvironment, and have been the subject of much research in the past decade. This review examines the relationship between PaSCs and cancer cells. METHODS: A comprehensive literature search was performed of multiple databases up to March 2014, including Medline, Pubmed and Google Scholar. RESULTS: A complex bidirectional interplay exists between PaSCs and cancer cells, resulting in a perpetuating loop of increased activity and an overriding pro-tumorigenic effect. This involves a number of signalling pathways that also impacts on other stromal components and vasculature, contributing to chemoresistance. The Reverse Warburg Effect is also introduced as a novel concept in tumour stroma. CONCLUSION: This review highlights the pancreatic tumour microenvironment, and in particular PaSCs, as an ideal target for therapeutics. There are a number of cellular processes involving PaSCs which could hold the key to more effectively treating pancreatic cancer. The feasibility of targeting these pathways warrant further in depth investigation, with the aim of reducing the aggressiveness of pancreatic cancer and improving chemodelivery.
BACKGROUND: The prognosis of pancreatic cancer remains desperately poor, with little progress made over the past 30 years despite the development of new combination chemotherapy regimens. Stromal activity is especially prominent in the tissue surrounding pancreatic tumours, and has a profound influence in dictating tumour development and dissemination. Pancreatic stellate cells (PaSCs) have a key role in this tumour microenvironment, and have been the subject of much research in the past decade. This review examines the relationship between PaSCs and cancer cells. METHODS: A comprehensive literature search was performed of multiple databases up to March 2014, including Medline, Pubmed and Google Scholar. RESULTS: A complex bidirectional interplay exists between PaSCs and cancer cells, resulting in a perpetuating loop of increased activity and an overriding pro-tumorigenic effect. This involves a number of signalling pathways that also impacts on other stromal components and vasculature, contributing to chemoresistance. The Reverse Warburg Effect is also introduced as a novel concept in tumour stroma. CONCLUSION: This review highlights the pancreatic tumour microenvironment, and in particular PaSCs, as an ideal target for therapeutics. There are a number of cellular processes involving PaSCs which could hold the key to more effectively treating pancreatic cancer. The feasibility of targeting these pathways warrant further in depth investigation, with the aim of reducing the aggressiveness of pancreatic cancer and improving chemodelivery.
Authors: Carlos A Orozco; Neus Martinez-Bosch; Pedro E Guerrero; Judith Vinaixa; Tomás Dalotto-Moreno; Mar Iglesias; Mireia Moreno; Magdolna Djurec; Françoise Poirier; Hans-Joachim Gabius; Martin E Fernandez-Zapico; Rosa F Hwang; Carmen Guerra; Gabriel A Rabinovich; Pilar Navarro Journal: Proc Natl Acad Sci U S A Date: 2018-04-03 Impact factor: 11.205
Authors: Jonas R M Van Audenaerde; Jorrit De Waele; Elly Marcq; Jinthe Van Loenhout; Eva Lion; Johan M J Van den Bergh; Ralf Jesenofsky; Atsushi Masamune; Geert Roeyen; Patrick Pauwels; Filip Lardon; Marc Peeters; Evelien L J Smits Journal: Oncotarget Date: 2017-05-25