Cancer and the tumor microenvironment: a review of an essential relationship

Abstract

Purpose: The role of the microenvironment during the initiation and progression of carcinogenesis is now realized to be of critical importance, both for enhanced understanding of fundamental cancer biology, as well as exploiting this source of relatively new knowledge for improved molecular diagnostics and therapeutics.

Methods: This review focuses on: (1) the approaches of preparing and analyzing secreted proteins, (2) the contribution of tumor microenvironment elements in cancer, and (3) the potential molecular targets for cancer therapy.

Results: The microenvironment of a tumor is an integral part of its physiology, structure, and function. It is an essential aspect of the tumor proper, since it supplies a nurturing environment for the malignant process. A fundamental deranged relationship between tumor and stromal cells is essential for tumor cell growth, progression, and development of life threatening metastasis. Improved understanding of this interaction may provide new and valuable clinical targets for cancer management, as well as risk assessment and prevention. Non-malignant cells and secreted proteins from tumor and stromal cells are active participants in cancer progression.

Conclusions: Monitoring the change in the tumor microenvironment via molecular and cellular profiles as tumor progresses would be vital for identifying cell or protein targets for cancer prevention and therapy.

Fig. 1. Carcinogenesis

a A well-differentiated stratified epithelium is separated from the stromal compartment by a well delineated basement membrane. The stromal compartment essentially consists of fibroblasts, leukocytes (monocytes and macrophages), collagen bundles and mature blood vessels. b During carcinogenesis, both epithelial and stromal components initially undergo modifications that promote epithelial cell propagation and mutation. Fibroblast becomes activated while the number of macrophages increases. Transient angiogenesis occurs with new vasculature similar to the one with normal epithelia. c Proliferation of epithelial cells with the development of an activated stroma is associated with the progression to carcinoma. Hence, extracellular-matrix components such as collagen are degraded, the number of inflammatory cells increases and fibroblasts differentiate to myofibroblasts resulting in the expression of growth factors, matrix components and degrading proteases. Angiogenesis is maintained resulting in the development of new blood vessels. Cells and molecular components of the microenvironment are targets for chemopreventive or therapeutic agents at all steps shown