Treatment with Cannabinoids as a Promising Approach for Impairing Fibroblast Activation and Prostate Cancer Progression
Cannabinoids are lipids that can regulate multiple biological processes by interacting with cell-surface cannabinoid receptors, namely CB1 and CB2. Noticeably, these receptors are up-regulated in malignant tissues compared to healthy tissues and a correlation between their higher expression and poorer disease prognosis is proven for many cancers. In the case of prostate cancer, both CB1 and CB2 have been identified as regulators of tumorous cells proliferation, invasion and migration to other organs (the process underlying metastasis).
However, to date, it is widely accepted that cancer outcome does not only depend on the behavior of cancer cells, but also on the tumor microenvironment (TME) that nourish proliferation and support migrations of the cancer cells. In prostate cancer particularly, cancer associated fibroblasts (CAFs) is the most abundant stromal cells, playing an essential role during all stages of disease progression, including metastasis. Patient-derived prostate CAFs also have higher CB1 and CB2 expression than normal fibroblasts (HPFs). Thus, it is crucial that cancer therapy targets all components of the TME.
A growing body of evidence in the last few decades has supported cannabinoids’ ability to influence cancer progression in models of human cancers. Specifically in prostate cancer, cannabinoids exhibit anti-proliferative and anti-invasive effects of cancerous cells. Furthermore, a synthetic cannabinoid has recently also been demonstrated to impair activities of CAFs, preventing them from supplying nutrients for and supporting invasion of tumors. Because of these findings, which highlight that they can simultaneously attack cancer and stromal cells, cannabinoids are increasingly recognized as promising anti-cancer drugs, especially in prostate cancer patients.