Cannabinoids, their cellular receptors, and effects on the invasive phenotype of carcinoma and metastasis

Abstract

Background: The morbidity and mortality of cancer are significantly impacted by the invasive and metastatic potential of particular subgroups of malignant cells within a tumor. The particular pre-metastatic properties of cancerous cells are thus a critical target for novel therapeutics in the oncology field. Cannabinoid molecules have been investigated in recent years in the context of invasion and metastasis of various malignancies, with varying effects reported in the literature.Recent Findings: There was substantial variability in the findings reported by the literature of the effects of cannabinoid molecules on cancer cell invasion and metastasis. These effects varied depending on which ligand and which of the CB1, CB2, or GPR55 receptors were investigated. These findings suggest a role for the phenomenon of biased signaling in explaining the diversity of effects of cannabinoid molecules on cancer cell invasion. Conclusion:While substantially more investigation is required into the effects of cannabinoid molecules on cancer cell invasion and metastasis, we describe in this review the significant diversity in the responses of cancer cells to cannabinoid molecules in terms of their invasive and metastatic capacities.

The evolution of cannabinoid receptors in cancer

“…Thus making it a promising anti-tumorigenic therapeutic treatment (Moreno et al, 2019). (Glogauer & Blay, 2022;Lynch, 2005;Valeri & Mazzon, 2021;Xian et al, 2010) (Nithipatikom et al, 2004;Pagano et al, 2021;Pietrovito et al, 2020;Roberto et al, 2019; (Hinz & Ramer, 2022;Liu et al, 2020;Lynch, 2005) (Pagano et al, 2021) In prostate and breast cancer cells, CB2R can heterodimerize with GPCR C-X-C chemokine receptor type 4 (CXCR4) (Laezza et al, 2020;Moreno et al, 2019). CXCR4 is associated with metastatic mechanisms as it can regulate proliferation and migration causing local and distant metastatic invasion (Laezza et al, 2020;Moreno et al, 2019).…”

Targeting the Endocannabinoidome in Pancreatic Cancer

“…Cannabinoid CB 1 and CB 2 receptors play a part in pancreatic cancer through differing pathways. Promiscuity in these receptor-mediated effects is due to biased agonism of cannabinoid GPCR receptors, which can modulate their shape when bound to different endocannabinoid ligands, and effectuate multiple effects [ 69 ].…”

Essential Dynamics of CB1Receptor-Agonist Complexes: Implications for Signalling Bias

“…The cannabinoid CB 1 G protein-coupled receptor (GPCR) is primarily expressed in the central nervous system, and as part of the endocannabinoid system (ECS) is linked with a number of metabolic or neurodegenerative processes and disorders including obesity, depression, learning, pain, Parkinson’s disease and cancer 1,2 . Many studies have explored the potential therapeutic applications of CB 1 ligands, 3 but these efforts have been hampered by the incidence of adverse effects including psychiatric disorders.…”