Gravity-based microfiltration reveals unexpected prevalence of circulating tumor cell clusters in ovarian and colorectal cancer
Abstract 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 W...
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Nature Portfolio
2025-02-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-024-00702-9 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Anne Meunier |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-191e72a5f5e84e7fbe5f069852e922ec |
| institution | Kabale University |
| issn | 2730-664X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Medicine |
| spelling | doaj-art-191e72a5f5e84e7fbe5f069852e922ec2025-02-09T12:52:06ZengNature PortfolioCommunications Medicine2730-664X2025-02-015111710.1038/s43856-024-00702-9Gravity-based microfiltration reveals unexpected prevalence of circulating tumor cell clusters in ovarian and colorectal cancerAnne Meunier0Javier Alejandro Hernández-Castro1Nicholas Chahley2Laudine Communal3Sara Kheireddine4Newsha Koushki5Nadia Davoudvandi6Sara Al Habyan7Benjamin Péant8Anthoula Lazaris9Andy Ng10Teodor Veres11Luke McCaffrey12Diane Provencher13Peter Metrakos14Anne-Marie Mes-Masson15David Juncker16Biomedical Engineering Department, McGill UniversityBiomedical Engineering Department, McGill UniversityBiomedical Engineering Department, McGill UniversityInstitut du cancer de Montréal and Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM)Biomedical Engineering Department, McGill UniversityBiomedical Engineering Department, McGill UniversityBiomedical Engineering Department, McGill UniversityRosalind and Morris Goodman Cancer Institute, McGill UniversityInstitut du cancer de Montréal and Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM)Cancer Research Program, The Research Institute of McGill University Health CenterBiomedical Engineering Department, McGill UniversityBiomedical Engineering Department, McGill UniversityRosalind and Morris Goodman Cancer Institute, McGill UniversityInstitut du cancer de Montréal and Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM)Cancer Research Program, The Research Institute of McGill University Health CenterInstitut du cancer de Montréal and Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM)Biomedical Engineering Department, McGill UniversityAbstract 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.https://doi.org/10.1038/s43856-024-00702-9 |
| spellingShingle | 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 Gravity-based microfiltration reveals unexpected prevalence of circulating tumor cell clusters in ovarian and colorectal cancer Communications Medicine |
| title | Gravity-based microfiltration reveals unexpected prevalence of circulating tumor cell clusters in ovarian and colorectal cancer |
| title_full | Gravity-based microfiltration reveals unexpected prevalence of circulating tumor cell clusters in ovarian and colorectal cancer |
| title_fullStr | Gravity-based microfiltration reveals unexpected prevalence of circulating tumor cell clusters in ovarian and colorectal cancer |
| title_full_unstemmed | Gravity-based microfiltration reveals unexpected prevalence of circulating tumor cell clusters in ovarian and colorectal cancer |
| title_short | Gravity-based microfiltration reveals unexpected prevalence of circulating tumor cell clusters in ovarian and colorectal cancer |
| title_sort | gravity based microfiltration reveals unexpected prevalence of circulating tumor cell clusters in ovarian and colorectal cancer |
| url | https://doi.org/10.1038/s43856-024-00702-9 |
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