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Real-time monitoring of circulating tumor cell (CTC) release after nanodrug or tumor radiotherapy using in vivo flow cytometry.

ABSTRACT: Noninvasive biological readouts of tumor metastatic risk and therapeutic efficacy are needed as healthcare costs rise. CTCs are the source of metastasis in distant organs that are responsible for the majority of cancer-related deaths. Here we demonstrate the acute and long-term effect of vascular disrupting therapies (high-dose radiotherapy and tumor necrosis factor-alpha (TNF)) on CTCs released from the primary tumor with a non-invasive real-time in vivo flow cytometry system. Using our innovative flow cytometry platform, we show here that radiation and nanodrug treatment can lead to short term release of CTC from the primary tumor. There was no increase in metastasis frequency or extent between control and TNF-treated mice; however, a significant reduction in lung metastasis was noted in the radiotherapy alone group. Mice treated with both TNF and radiotherapy had a slightly elevated metastatic profile between that of radiation alone and control (untreated) tumors. Possible mechanisms based on therapy specific vessel disruption and cell death are discussed. Overall, CTCs correlated with tumor progression and suggest CTC enumeration described herein may be useful in clinical management of solid tumor malignancies.

SUBMITTER: Koonce NA

PROVIDER: S-EPMC5743220 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Real-time monitoring of circulating tumor cell (CTC) release after nanodrug or tumor radiotherapy using in vivo flow cytometry.

Koonce Nathan A NA Juratli Mazen A MA Cai Chengzhong C Sarimollaoglu Mustafa M Menyaev Yulian A YA Dent Judith J Quick Charles M CM Dings Ruud P M RPM Nedosekin Dmitry D Zharov Vladimir V Griffin Robert J RJ

Biochemical and biophysical research communications 20170816 3

Noninvasive biological readouts of tumor metastatic risk and therapeutic efficacy are needed as healthcare costs rise. CTCs are the source of metastasis in distant organs that are responsible for the majority of cancer-related deaths. Here we demonstrate the acute and long-term effect of vascular disrupting therapies (high-dose radiotherapy and tumor necrosis factor-alpha (TNF)) on CTCs released from the primary tumor with a non-invasive real-time in vivo flow cytometry system. Using our innovat ...[more]

PMID: 28822765

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Project description:BackgroundContemporary cancer diagnostics are becoming increasing reliant upon sophisticated new molecular methods for analyzing genetic information. Limiting the scope of these new technologies is the lack of adequate solid tumor tissue samples. Patients may present with tumors that are not accessible to biopsy or adequate for longitudinal monitoring. One attractive alternate source is cancer cells in the peripheral blood. These rare circulating tumor cells (CTC) require enrichment and isolation before molecular analysis can be performed. Current CTC platforms lack either the throughput or reliability to use in a clinical setting or they provide CTC samples at purities that restrict molecular access by limiting the molecular tools available.Methodology/principal findingsRecent advances in magetophoresis and microfluidics have been employed to produce an automated platform called LiquidBiopsy®. This platform uses high throughput sheath flow microfluidics for the positive selection of CTC populations. Furthermore the platform quantitatively isolates cells useful for molecular methods such as detection of mutations. CTC recovery was characterized and validated with an accuracy (<20% error) and a precision (CV<25%) down to at least 9 CTC/ml. Using anti-EpCAM antibodies as the capture agent, the platform recovers 78% of MCF7 cells within the linear range. Non specific recovery of background cells is independent of target cell density and averages 55 cells/mL. 10% purity can be achieved with as low as 6 CTCs/mL and better than 1% purity can be achieved with 1 CTC/mL.Conclusions/significanceThe LiquidBiopsy platform is an automated validated platform that provides high throughput molecular access to the CTC population. It can be validated and integrated into the lab flow enabling CTC enumeration as well as recovery of consistently high purity samples for molecular analysis such as quantitative PCR and Next Generation Sequencing. This tool opens the way for clinically relevant genetic profiling of CTCs.

Dataset Information

Real-time monitoring of circulating tumor cell (CTC) release after nanodrug or tumor radiotherapy using in vivo flow cytometry.

Publications

Real-time monitoring of circulating tumor cell (CTC) release after nanodrug or tumor radiotherapy using in vivo flow cytometry.

Similar Datasets

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