In the past century, gradual but sustained advances in our understanding of the molecular mechanisms involved in the growth and invasive properties of cancer cells have led to better management of tumors. However, many tumors still escape regulation and progress to advanced disease. Until recently, there has not been an organized and sustained focus on the "normal" cells in the vicinity of tumors. Interactions between the tumor and these host cells, as well as autonomous qualities of the host cells themselves, might explain why tumors in people with histologically similar cancers often behave and respond differently to treatment. Cells of the tumor microenvironment, variously referred to as cancer stroma, reactive stroma or carcinoma-associated fibroblasts (CAF), exist in close proximity to the cancer epithelium. Both stromal and epithelial phenotypes co-evolve during tumorigenesis and it is now becoming clear that these stromal cells may not be the innocent bystanders they had been widely thought to be, but rather may be active contributors to carcinogenesis. Our group and others have shown the important role that CAF play in the progression of cancer. In this article we will address current trends in the study of the interactions between cancer stroma and tumor cells in different organs. We will also highlight perceived knowledge gaps and suggest research areas that need to be further explored to provide new targets for anticancer therapies.
Bibliographical noteFunding Information:
The authors acknowledge funding from the National Cancer Institute via grants U54 CA113007 and U54 CA126505. We also thank the Frances Williams Preston Laboratories of the TJ Martell Foundation for support. The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Copyright 2017 Elsevier B.V., All rights reserved.
- Activated fibroblasts
- Cancer associated fibroblast
- Stromal-epithelial interaction
- Tumor heterogeneity
- Tumor stroma