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Clinical Microfluidic Chip Platform for the Isolation of Versatile Circulating Tumor Cells
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Functional Analysis of Viable Circulating Tumor Cells from Triple-Negative Breast Cancer Patients Using TetherChip

Vasileios Vardas1, Julia A Ju2, Athina Christopoulou3

  • 1Laboratory of Biochemistry/Metastatic Signaling, Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, GR-26504 Patras, Greece.

Cells
|August 11, 2023
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Summary

This study isolated viable circulating tumor cells (CTCs) from triple-negative breast cancer (TNBC) patients. A novel method using TetherChip technology effectively evaluated drug responses, showing vinorelbine induces apoptosis and reduces metastasis markers in CTCs.

Keywords:
EMTcirculating tumor cellsimmune checkpointsmetastasistriple-negative breast cancervinorelbine

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Area of Science:

  • Oncology
  • Cell Biology
  • Translational Medicine

Background:

  • Metastasis is the primary cause of breast cancer mortality, with triple-negative breast cancer (TNBC) being particularly aggressive.
  • Microtentacles (McTNs) are crucial for metastasis, and TNBC lacks effective targeted therapies.
  • Isolating and functionally analyzing viable circulating tumor cells (CTCs) is essential for personalized treatment strategies.

Purpose of the Study:

  • To isolate viable CTCs from TNBC patients for functional drug analysis.
  • To evaluate the efficacy of vinorelbine in inducing apoptosis and reducing metastasis-associated markers in CTCs.
  • To establish a patient-individualized method for targeting metastatic dissemination.

Main Methods:

  • CTCs were isolated from 20 TNBC patients using TetherChip technology and cultured for 5 days.
  • Biomarker expression (Detyrosinated α-tubulin, PD-L1) was assessed via immunofluorescence and VyCap analysis.
  • Vinorelbine-induced apoptosis was quantified by M30-positive cell detection.

Main Results:

  • TetherChips significantly increased CTC yield compared to cytospins (p = 0.006), enabling drug evaluation.
  • One-hour vinorelbine treatment induced significant apoptosis in live CTCs (p = 0.010).
  • Vinorelbine significantly reduced Detyrosinated α-tubulin and PD-L1 expression (p < 0.001) and disrupted McTNs.

Conclusions:

  • TetherChip technology provides a viable protocol for functional CTC analysis and drug efficacy assessment.
  • This approach offers critical insights for developing individualized therapies against metastatic breast cancer.
  • Targeting metastatic dissemination at a patient-specific level is achievable with this methodology.