By Study Targets Cancer Cell Plasticity
Researchers published a new study in Communications Biology exploring how cannabis compounds affect breast cancer. The team focused on the plasticity of cancer cells, which allows them to revert to immature states.
Such resistance often leads to more aggressive and proliferative tumor growth.
The study utilized organoids, which are lab-built 3D mammary tumor models. These models were created from human breast cancer cells and mouse models.
They noted that this system regulates processes paralleled in both cancer evolution and embryonic development.
The experiment targeted two main cannabinoid receptors, CB1R and CB2R. The team used specific ligands to either boost or block the activity of these receptors. This approach allowed them to isolate the biological responses triggered by each receptor type.
The goal was to determine which receptor plays a critical role in tumor behavior.
Low-Dose THC Reduces Aggression
Scientists administered an ultra-low-dose, 4-day pulse of THC to the organoids. After this short treatment period, the organoids exhibited reduced cell invasiveness.
The cells also showed lower self-renewal capabilities and decreased tumor initiation rates.
The results indicated that the effects were mediated predominantly by the CB2R receptor. This receptor is associated with inflammatory responses rather than psychoactive effects. The CB1R receptor, linked to cannabis’ psychoactive properties, did not show the same impact.
This distinction highlights the specific biological pathway involved in the observed changes.
Researchers also tested inverse agonists called SR1 and SR2 to reduce baseline receptor activity. The CB2R inverse agonist SR2 reproduced the cancer-mollifying effects seen with THC. In contrast, the CB1R inverse agonist SR1 did not produce similar results.
Organoids from mice genetically engineered to lack CB2R also showed similar changes, suggesting baseline activity is key.
In Vivo Results Show Stability
The researchers found evidence that the tumor-inhibiting effects are stable in living organisms. They transplanted the THC-treated organoids into living cancer-prone mice. The effects persisted for up to 100 days in these animals.
This duration demonstrates the long-term potential of the observed biological changes.
Mice receiving the treated organoids developed tumors later than those receiving control organoids. These animals also showed slower tumor growth overall. The lesions observed were less aggressive compared to the control group.
This outcome supports the idea that manipulating receptor activity can influence tumor progression.
In a separate experiment, THC-treated cells produced fewer clusters of cancer cells in the lungs. This measurement was taken four weeks after injection into the mice. The modulated organoids also showed resilience when researchers tried to increase their tumor-forming activity.
The researchers explain that controlling this process could influence differentiated cells to occupy space and resources that would otherwise be used for tumor expansion.
