The mesenchyme in malignancy: A partner in the initiation, progression and dissemination of cancer

The tumor microenvironment presents an exciting opportunity for innovative prognostic and therapeutic approaches to human cancer. The diverse cellular and extracellular contribution to tumor growth argues that prevention and cure of human cancers will result only from a multifaceted approach to cancer therapy. In this review we provide a foundation for considering the mesenchymal contribution to the tumor microenvironment. We address normal mesenchymal development, physiological interactions between the epithelium and stroma and the cellular hierarchy within these compartments. We focus on cancer-associated fibroblasts in gastrointestinal malignancy but our models have also been informed by other tumor systems. The review provides a framework for characterizing the overall biological contribution of the mesenchyme to human disease. Understanding the biological heterogeneity of specific mesenchymal cells in cancer will provide new opportunities for targeted cancer prevention and therapy.