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Acoustic enrichment of heterogenous circulating tumor cells and clusters from patients with metastatic prostate cancer.
Magnusson, Cecilia; Augustsson, Per; Anand, Eva Undvall; Lenshof, Andreas; Josefsson, Andreas; Welén, Karin; Bjartell, Anders; Ceder, Yvonne; Lilja, Hans; Laurell, Thomas.
Afiliación
  • Magnusson C; Department of Translational Medicine, Lund University, Lund, Sweden.
  • Augustsson P; Department of Biomedical Engineering, Lund University, Lund, Sweden.
  • Anand EU; Department of Biomedical Engineering, Lund University, Lund, Sweden.
  • Lenshof A; Department of Biomedical Engineering, Lund University, Lund, Sweden.
  • Josefsson A; Intitute of Clinical Sciences, Department of Urology, Gothenburg University, Gothenburg Sweden.
  • Welén K; Wallenberg Center for Molecular Medicine, Umeå University, Umeå, Sweden.
  • Bjartell A; Department of Urology and Andrology, Institute of surgery and perioperative Sciences, Umeå University, Umeå, Sweden.
  • Ceder Y; Intitute of Clinical Sciences, Department of Urology, Gothenburg University, Gothenburg Sweden.
  • Lilja H; Department of Translational Cancer Research, Lund University, Lund, Sweden.
  • Laurell T; Department of Laboratory Medicine, Lund University, Lund, Sweden.
medRxiv ; 2023 Dec 04.
Article en En | MEDLINE | ID: mdl-38106097
ABSTRACT

Background:

There are important unmet clinical needs to develop cell enrichment technologies to enable unbiased label-free isolation of both single cell and clusters of circulating tumor cells (CTCs) manifesting heterogeneous lineage specificity. Here, we report a pilot study based on microfluidic acoustophoresis enrichment of CTCs using the CellSearch CTC assay as a reference modality.

Methods:

Acoustophoresis uses an ultrasonic standing wave field to separate cells based on biomechanical properties (size, density, and compressibility) resulting in inherently label-free and epitope-independent cell enrichment. Following red blood cell lysis and paraformaldehyde fixation, 6 mL of whole blood from 12 patients with metastatic prostate cancer and 20 healthy controls were processed with acoustophoresis and subsequent image cytometry.

Results:

Acoustophoresis enabled enrichment and characterization of phenotypic CTCs (EpCAM+, Cytokeratin+, DAPI+, CD45-/CD66b-) in all patients with metastatic prostate cancer and detected CTC-clusters composed of only CTCs or heterogenous aggregates of CTCs clustered with various types of white blood cells in 9 out of 12 patients. By contrast, CellSearch did not detect any CTC-clusters, but detected comparable numbers of phenotypic CTCs as acoustophoresis, with trends of finding higher number of CTCs using acoustophoresis.

Conclusion:

Our preliminary data indicate that acoustophoresis provides excellent possibilities to detect and characterize CTC-clusters as a putative marker of metastatic disease and outcomes. Moreover, acoustophoresis enables sensitive label-free enrichment of cells with epithelial phenotype in blood and offers opportunities to detect and characterize CTCs undergoing epithelial-to-mesenchymal transitioning and lineage plasticity.
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: MedRxiv Año: 2023 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: MedRxiv Año: 2023 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos