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Chemotherapy-induced release of circulating-tumor cells into the bloodstream in collective migration units with cancer-associated fibroblasts in metastatic cancer patients


Ortiz-Otero NNerymar , Marshall JRJocelyn R , Lash BBradley , King MRMichael R . BMC cancer. 2020 9 11; 20(1). 873


BACKGROUND: Recent studies have shown that chemotherapy destabilizes the blood vasculature and increases circulating tumor cell (CTC) influx into the circulation of metastatic cancer patients (Met-pa). CTCs are a precursor of cancer metastasis, in which they can migrate as single CTCs or as CTC clusters with stromal cells such as cancer-associated fibroblasts (CAFs) as cell aggregates.

METHODS: Blood samples were collected from 52 Met-pa, and the number of CTC and CAF was determined along with the temporal fluctuation of these through the chemotherapy treatment.

RESULTS: In this study, CTC level was found to increase two-fold from the initial level after 1 cycle of chemotherapy and returned to baseline after 2 cycles of chemotherapy. Importantly, we determined for the first time that circulating CAF levels correlate with worse prognosis and a lower probability of survival in Met-pa. Based on the CTC release induced by chemotherapy, we evaluated the efficacy of our previously developed cancer immunotherapy to eradicate CTCs from Met-pa blood using an ex vivo approach and demonstrate this could kill over 60% of CTCs.

CONCLUSION: Collectively, we found that CAF levels in Met-pa serve as a predictive biomarker for cancer prognosis. Additionally, we demonstrate the efficacy of our therapy to kill primary CTCs for a range of cancer types, supporting its potential use as an anti-metastasis therapy in the clinical setting.