Extracellular TROP2 Fragment Identified as a Potential Biomarker and Metastasis Driver

Cancer research · Prostate cancer · EGFR

Shed TROP2 extracellular domain (TCD) binds and activates EGFR signaling, promoting prostate cancer metastasis

This study demonstrates that the extracellular domain of TROP2 (TCD) is shed from prostate cancer cells, circulates in serum, binds to EGFR, and activates downstream PI3K/AKT/mTOR signaling pathways. In vitro assays show that TCD overexpression enhances migration and invasion of prostate cancer cells without affecting proliferation, while in vivo models reveal increased spontaneous metastasis after recombinant TCD administration. Mass‑spectrometry confirms the TCD–EGFR interaction, and EGFR inhibitors abrogate TCD‑driven invasion. Elevated serum TCD levels distinguish patients with recurrent disease from non‑recurrent or cancer‑free controls, supporting its potential as a liquid biomarker. The authors also report the development of anti‑TROP2 antibodies that block shedding, offering a therapeutic avenue for TROP2‑positive malignancies.

The identification of TCD as a circulating biomarker and an actionable driver of metastasis provides a novel avenue for risk stratification and targeted therapy in prostate cancer, a disease with limited prognostic tools for metastatic progression.

Evidence level: Állatkísérletes. Állatmodellben vizsgálták.

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