Increasing circulating exosomes‐carrying TRPC5 predicts chemoresistance in metastatic breast cancer patients

Abstract

Chemoresistance, the major obstacle in breast cancer chemotherapy, results in unnecessary chemotherapy and wasting of medical resources. No feasible method has been available to predict chemoresistance before chemotherapy. In our previous study, elevated expression of transient receptor potential channel TRPC5 was found to be an essential element for chemoresistance in breast cancer cells, and it was determined that it could be transferred to chemosensitive breast cancer cells through releasing extracellular vesicles (EV) containing TRPC5 from chemoresistant cells, resulting in acquired chemoresistance. Exosomes, a type of EV, are secreted membrane‐enclosed vesicles of 50–150‐nm diameter. In this study we found that circulating exosomes in peripheral blood from breast cancer patients carried TRPC5. In the present study, circulating exosome‐carrying TRPC5 (cirExo‐TRPC5) level was significantly correlated with TRPC5 expression level in breast cancer tissues and tumor response to chemotherapy. Furthermore, increased cirExo‐TRPC5 level after chemotherapy preceded progressive disease (PD) based on imaging examination and strongly predicted acquired chemoresistance. Taken together, our study demonstrated that cirExo‐TRPC5 might act as a noninvasive chemoresistance marker and might serve as an adjuvant to the current imaging examination‐based chemoresistance.

Elevated levels of extracellular vesicles are associated with therapy failure and disease progression in breast cancer patients undergoing neoadjuvant chemotherapy

“…In vitro studies suggested a similar tendency by demonstrating a chemotherapy resistance transfer and neutralizing anti-HER2 treatment by EVs. [21][22][23][24]33 Post-NACT EV concentrations were associated with BC outcome of a reduced 3y-PFS and OS. Of note, the same cut-off value for EV concentrations post-NACT was obtained regarding 3y-PFS and OS for patient stratification.…”

“…20 Further, BC-derived EVs can mediate drug resistance transfer from chemotherapy resistant BC cells to non-resistant BC cells via P-Glycoproteins or micro-RNAs. [21][22][23] Additionally, BC specific targeted drugs are reported to be neutralized by EVs expressing the drugs' target protein. 24 Clinical studies analyzing tumor-derived EVs associated biomarkers have been conducted for quite a few tumor entities.…”

Exploring the key communicator role of exosomes in cancer microenvironment through proteomics

“…Secondly, there is a large amount of drug and chemoresistance proteins in the exosome. GSTP1, TGF-β1, TPRC5, and UCH-L1 are examples [97][98][99][100]. Finally, proteins that induce metastasis present highly in exosomes.…”

“…Drug and chemotherapy resistance [97] TGF-β1 Drug resistance [98] TPRC5 Chemotherapy resistance [99] UCH-L1 Chemotherapy resistance [100] Nephronectin Induce tumor mestasis [101] Caveolin-1 Enriched in metastasized cancer cell [36] Periostin Enriched in metastasized cancer cell [102] Myoferlin Enriched in metastasized cancer cell [31] Lung Cancer Mucin 5AC, B Lung cancer relapse and metastasis [103,104] Desmoglein-2 overspressed in non small cell lung cancer and induce cell growth [105] EGFR Oncogene in lung cancer [106,111,113,114] LRG1 Induce angiogenesis [108] Tim-3 Induce anti-tumor immune response [110] NY-SEO-1 Overexpressed in lung cancer [111] [111] EpCam Overexpressed in lung cancer [111] SGRN Overexpressed in lung cancer [112] TPM3 Overexpressed in lung cancer [112] THBS1 Overexpressed in lung cancer [112] HUWE1 Overexpressed in lung cancer [112] MUC 1 Overexpressed in lung cancer [112] Colon Cancer…”

Investigating the Potential and Pitfalls of EV-Encapsulated MicroRNAs as Circulating Biomarkers of Breast Cancer

“…Initially deemed a mechanism of cellular waste disposal, extracellular vesicles (EVs) secreted by cells are now known to encapsulate a variety of biomolecules thought to be reflective of the cell from which they are released [1]. As such, they hold significant potential as circulating biomarkers of disease, with proposed applications in cancer diagnosis, prognostication, and prediction or monitoring of response to therapy [1][2][3][4][5][6][7]. However, rapid expansion in the field, as evidenced by a surge in publications, is not without challenges.…”