Thyroid Hormone Activation Regulates the Crosstalk between Breast Cancer and Mesenchymal Stem Cells.

Summary

Breast cancer cells increased intracellular thyroid hormone activation via D2, enhancing EMT features and pro-tumorigenic crosstalk with mesenchymal stem cells; genetic D2 inactivation reduced invasiveness and MSC-driven induction. Findings from co-culture and intraductal in vivo modeling nominate D2 as a therapeutic target.

Key Findings

• MCF7 breast cancer cells enhanced intracellular thyroid hormone activation via DIO2, promoting EMT traits.
• DIO2 inactivation reduced invasiveness and dampened responsiveness to mesenchymal stem cell–mediated pro-tumor induction.
• Use of co-culture with primary human MSCs and an intraductal (MIND) in vivo approach supported the role of D2 in tumor–stroma crosstalk.

Clinical Implications

If validated in vivo and clinically, D2 inhibition could attenuate EMT and stromal pro-tumor signaling in hormone-responsive breast cancer; thyroid status and TH activation may warrant consideration in tumor management.

Limitations

• Findings are preclinical; clinical relevance and safety of D2 inhibition remain untested.
• Evidence reported in an ER+ cell line context; generalizability across breast cancer subtypes is uncertain.

Future Directions

Evaluate pharmacologic D2 inhibitors in orthotopic and metastatic models, define downstream EMT and stromal signaling circuits, and explore biomarker strategies for patient selection.