Components of the Tumor Microenvironment
The tumor microenvironment is all of the surrounding space in which a tumor lies. This includes the organ of residence, the surrounding stroma, the surrounding stroma cells/vasculature and potentially the bone. All of these components can contribute to disease spread and are important variables to consider when studying cancer. Here I will highlight some key components to the tumor microenvironment for various cancers.
1. Organ of residence
Depending on the tumor type, where the carcinoma develops has key insight into how easily a cancer can manifest. One example, humans often develop tumors in sex organs like the breasts or prostate because of the abundance of hormones that can induce growth. Another example is that certain pathogens can only infect certain tissues. Chronic H. pylori infection in the stomach can lead to stomach ulcers and cancer. Chronic HPV infection, a virus that mainly attacks basal keratinocytes like in the cervix, is the main agent responsible for cervical cancer. (There is an HPV vaccine—get it if eligible and definitely encourage teenagers to get it!!) Finally, liquid cancers like leukemia also have high manifestation because they start out already in an area (blood vessels).
2. The surrounding stroma
The stroma is defined as the supportive tissue of an organ. In cell biology, many people learn about the extra-cellular matrix (ECM). This as well as fat, nerves and blood vessels make up the stroma. The purpose is to protect organs from the mechanical stress of moving the body. It, to some extent, can block cancer cells from migrating due to the density of the tissue. Tumors have to secrete (or induce the secretion of) enzymes called matrix metalloproteinases (MMPs) in order to break down the dense stroma and invade the ECM.
3. The stromal cells
There are many cells in the stroma whose purposes are to prevent infections of the organs, secrete collagen to maintain matrix integrity and to line the blood vessels.
- Cells that prevent infection are called immune cells. Common immune cells in the tumor stroma include T cells, B cells and macrophages. These cells are capable of recognizing a tumor, but because cancer is a disease of self (and T and B cells largely have mechanisms to not attack native cells) they often recognize the tumors as ‘normal’. Macrophages, depending on polarization, can express pro- or anti-tumor activity. Classically polarized macrophages, known as M1 macrophages, can block tumor growth and spread by causing a cytotoxic environment. Alternatively activated macrophages, known as M2 macrophages, can induce tumor growth and spread by causing favorable tumor remodeling and secretion of factors that help induce angiogenesis (blood vessel growth into a tumor).
- Cells that make the ECM are called fibroblasts. Cancer-associated fibroblasts (CAFs) are not normal, however. Rather than primarily secreting collagen and other fibers like classic fibroblasts, CAFs primarily secrete MMPs to help turnover the ECM.
- Finally, endothelial cells that line blood vessels are present. When a tumor grows beyond 1mm in diameter, oxygen and nutrients become a limiting factor by diffusion. To combat the hypoxia, tumors induce angiogenesis. The endothelial cells lining existing vessels are activated by growth factors either from the tumor itself (or even from the stroma cells!) The endothelial cells do not form vessels with the structural integrity of most of the vasculature, providing a means for the tumor cells to invade and spread via vessels.