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Background <p>Circulating tumor cells (CTCs) are rare (a few cells per milliliter of blood) and mostly isolated as single-cell CTCs (scCTCs). CTC clusters (cCTCs), even rarer, are of growing interest, notably because of their higher metastatic potential, but very difficult to isolate.</p> Method <p>We introduce gravity-based microfiltration (GµF) for facile isolation of cCTCs using in-house fabricated microfilters and 3D printed cartridges. Optimal flow rate and pore size for cCTC isolation are determined by GµF of cultured ovarian single cells and cell clusters spiked in healthy blood. We perform GµF of blood from orthotopic ovarian cancer mouse models and characterize the morphological features of scCTCs and cCTCs, and the expression of molecular markers for aggressiveness. Finally, we analyze blood from 17 epithelial ovarian cancer patients with either localized or metastatic disease, and from 13 colorectal cancer liver metastasis patients.</p> Results <p>Here, we show that GµF optimized for cell cluster isolation captures cCTCs from blood while minimizing unwanted cluster disaggregation, with ~85% capture efficiency. We detect cCTCs in every patient, with between 2–100+ cells. We find cCTCs represent between 5–30% of all CTC capture events, and 10-80% of the CTCs are clustered; remarkably, in 10 patients, most CTCs are circulating not as scCTCs, but as cCTCs.</p> Conclusions <p>GµF uncovers the unexpected prevalence and frequency of cCTCs including sometimes very large ones in epithelial ovarian cancer patients, and motivates additional studies to uncover their properties and role in disease progression.</p>

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Gravity-based microfiltration reveals unexpected prevalence of circulating tumor cell clusters in ovarian and colorectal cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月3日

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  • Anne Meunier,
  • Javier Alejandro Hernández-Castro,
  • Nicholas Chahley,
  • Laudine Communal,
  • Sara Kheireddine,
  • Newsha Koushki,
  • Nadia Davoudvandi,
  • Sara Al Habyan,
  • Benjamin Péant,
  • Anthoula Lazaris,
  • Andy Ng,
  • Teodor Veres,
  • Luke McCaffrey,
  • Diane Provencher,
  • Peter Metrakos,
  • Anne-Marie Mes-Masson,
  • David Juncker

摘要

Background

Circulating tumor cells (CTCs) are rare (a few cells per milliliter of blood) and mostly isolated as single-cell CTCs (scCTCs). CTC clusters (cCTCs), even rarer, are of growing interest, notably because of their higher metastatic potential, but very difficult to isolate.

Method

We introduce gravity-based microfiltration (GµF) for facile isolation of cCTCs using in-house fabricated microfilters and 3D printed cartridges. Optimal flow rate and pore size for cCTC isolation are determined by GµF of cultured ovarian single cells and cell clusters spiked in healthy blood. We perform GµF of blood from orthotopic ovarian cancer mouse models and characterize the morphological features of scCTCs and cCTCs, and the expression of molecular markers for aggressiveness. Finally, we analyze blood from 17 epithelial ovarian cancer patients with either localized or metastatic disease, and from 13 colorectal cancer liver metastasis patients.

Results

Here, we show that GµF optimized for cell cluster isolation captures cCTCs from blood while minimizing unwanted cluster disaggregation, with ~85% capture efficiency. We detect cCTCs in every patient, with between 2–100+ cells. We find cCTCs represent between 5–30% of all CTC capture events, and 10-80% of the CTCs are clustered; remarkably, in 10 patients, most CTCs are circulating not as scCTCs, but as cCTCs.

Conclusions

GµF uncovers the unexpected prevalence and frequency of cCTCs including sometimes very large ones in epithelial ovarian cancer patients, and motivates additional studies to uncover their properties and role in disease progression.