The endocannabinoid system of the tumor stroma

Over the past centuries, Cannabis has been used as a traditional remedy for a variety of diseases before its recreational use was discovered in the 1920`s. With the advent of modern analytical methods, the main ingredients of the Cannabis plant were unraveled, and tetrahydrocannabinol was described as the main psychoactive component. It was soon established that this molecule activates brain cells via specific receptors, the so-called cannabinoid receptors. One of the most astonishing findings was that our organism is able to produce similar substances that would activate the cannabinoid receptors, hence, these substances were named endocannabinoids. Therefore, humans and animals alike have an endocannabinoid system, that regulates a variety of body functions such as hunger, appetite, emotions, and energy household. Next to these functions, it also plays a key role in inflammatory diseases, pain and cancer. Also, tumor growth can be influenced by endocannabinoids. Many cells in a tumor contain cannabinoid receptors, and today, endocannabinoids can be easily detected in tumor tissue. Tumors not only consist of tumor cells but also other cells like fibroblasts which are part of a structural connective framework called the tumor stroma. Fibroblasts in primary tumors are termed cancer associated fibroblasts and they constitute a prominent and hugely heterogeneous population. They have been associated with unfavorable prognosis in many cancers including lung and colon cancer. These cells express cannabinoid receptors and enzymes to respond to and to metabolize endocannabinoids. In the current project we investigate the role of the endocannabinoid system of the tumor stroma and ask whether it contributes to or inhibits tumor growth. We will investigate and measure endocannabinoids and cannabinoid receptors in tumor tissue and delineate their role in tumor progression. Cancer associated fibroblasts have been recently investigated as targets for antitumor therapy, however, with mixed outcomes. Since cannabinoid-based drugs are increasingly tested in clinical trials and because of the drugs good safety profiles, knowledge of the endocannabinoids` influence on tumor growth may open a way to a cannabinoid-based add- on antitumor therapy.