The Tumor Microenvironment

The tumor microenvironment comprises the tumor and the supporting tissue surrounding it, also known as the stroma. Tumor cells constantly interact with the stroma to form a permissive and supportive environment for their growth and metastasis.

The stroma consists of an extracellular matrix that surrounds the tumor and several cellular components.

The Extracellular Matrix, or ECM, is a complex network of macromolecules, including collagen and fibrin. Compared to normal tissues, the structure and composition of ECM in cancerous tissue are  modified to promote tumor progression.

For example, in breast cancer tissue, the increased expression of protease and oxidases degrade and linearize the dense network of cross-linked collagen fibers. This increases the stiffness of breast cancer tissue facilitating tumor cell migration.

The stroma also consists of Carcinoma-Associated Fibroblasts, or CAFs. They secrete several growth factors to aid cancer progression. For example, with the increase in tumor size, the demand for nutrients and oxygen increases. The innermost cancer cells in a solid tumor face acute oxygen limitation; a phenomenon called hypoxia.

CAFs secrete vascular endothelial growth factors that trigger the formation of new blood vessels around the growing tumor. This provides oxygen and nutrients to the rapidly dividing cells.

The immune cells, such as macrophages, lymphocytes, and natural killer cells, can detect the cancer cells and eliminate them. However, due to the increased genetic instability, cancer cells quickly acquire mutations to evade immune surveillance.

For example, tumor cells can induce immunosuppressive T-cells, which produce reactive oxygen species to inhibit the lymphocytes and prevent them from killing the tumor cells. The reactive oxygen species also increase the rate of mutations in tumor cells, facilitating rapid tumor progression.