An Ex vivo cultivation model for circulating tumor cells: The success rate and correlations with cancer response to therapy

I. Hsuan Chiang, Hsuan Chih Kuo, Chun Ta Liao, Yung Chia Kuo, Shao Ming Yu, Hung Ming Wang, Yi Hui Huang, Kim Anh Nguyen Thi, Min Hsien Wu, Jason Chia Hsun Hsieh*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

Abstract

BACKGROUND: Cancer mortality is closely linked to recurrence and distant metastasis, posing challenges in real-time tracking due to the invasiveness of current methods. Circulating tumor cells (CTCs) show promise as potential tools; however, their scarcity remains a significant obstacle.

METHOD: In this prospective study, we validated a simple culture protocol and investigated the correlation between clinical response and CTC growth status. Following negative selection, the isolated cells were subjected to ex vivo cultivation in a two-dimensional environment supplemented with cytokines for up to 21 days, followed by immunofluorescence staining for analysis.

RESULTS: Among 37 participants with solid tumors and distant metastasis (34.8% head and neck cancer), 47 samples were collected, from which CTCs were detected. The percentages of CTCs, atypical CTCs, and white blood cells during cultivation from days 7-21 were significantly different (p < 0.001, p < 0.001, and p = 0.330, respectively). Patients were further categorized into progressive disease (PD) and non-PD groups based on disease status, revealing significant differences in CTC growth rates, which increases from Days 7-21 between groups (5.5x vs. 2.8x growth, respectively; p < 0.001).

CONCLUSION: With the proposed protocols, we cultured CTCs from patients with various cancers for 21 days and identified a tool for predicting cancer response. The actual cancer status (PD or non-PD) at CTC isolation correlates to CTC growth rate, guiding the required observation time and parameters for culture.

Original languageEnglish
Article number100819
Pages (from-to)100819
JournalBiomedical Journal
Volume48
Issue number1
Early online date30 11 2024
DOIs
StatePublished - 02 2025

Bibliographical note

Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.

Keywords

  • CTC growth rate
  • Circulating tumor cells (CTCs)
  • Clinical response
  • Ex vivo culture
  • Negative selection

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