Moir John A G, Mann Jelena, White Steve A
Freeman Hospital, Department of HPB and Transplant Surgery, Newcastle upon Tyne, United Kingdom; Institute of Cellular Medicine, Fibrosis Lab, Newcastle upon Tyne, United Kingdom.
Institute of Cellular Medicine, Fibrosis Lab, Newcastle upon Tyne, United Kingdom.
Surg Oncol. 2015 Sep;24(3):232-8. doi: 10.1016/j.suronc.2015.05.002. Epub 2015 May 19.
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.
A comprehensive literature search was performed of multiple databases up to March 2014, including Medline, Pubmed and Google Scholar.
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.
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.
胰腺癌的预后仍然极其糟糕，尽管新的联合化疗方案不断发展，但在过去30年里几乎没有取得进展。基质活性在胰腺肿瘤周围组织中尤为突出，对肿瘤的发展和扩散有深远影响。胰腺星状细胞（PaSCs）在这种肿瘤微环境中起关键作用，并且在过去十年中一直是大量研究的主题。本综述探讨了PaSCs与癌细胞之间的关系。
截至2014年3月，对多个数据库进行了全面的文献检索，包括Medline、Pubmed和谷歌学术。
PaSCs与癌细胞之间存在复杂的双向相互作用，导致活性增加的持续循环和压倒性的促肿瘤作用。这涉及许多信号通路，这些通路也会影响其他基质成分和脉管系统，导致化疗耐药。反向瓦尔堡效应也作为肿瘤基质中的一个新概念被引入。
本综述强调胰腺肿瘤微环境，特别是PaSCs，是一个理想的治疗靶点。涉及PaSCs的许多细胞过程可能是更有效治疗胰腺癌的关键。靶向这些通路的可行性值得进一步深入研究，目的是降低胰腺癌的侵袭性并改善化疗药物递送。
