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Related Experiment Video

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Isolation and Propagation of Circulating Tumor Cells from a Mouse Cancer Model
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Identifying cancer origin using circulating tumor cells.

Si-Hong Lu1,2, Wen-Sy Tsai3, Ying-Hsu Chang4

  • 1a Graduate Institute of Life Sciences, National Defense Medical Center , Taiwan.

Cancer Biology & Therapy
|February 2, 2016
PubMed
Summary

This study introduces a new method using microfluidic chips and immunofluorescence staining to identify the primary cancer source of circulating tumor cells (CTCs) in blood. This breakthrough aids in early cancer detection and origin identification.

Keywords:
CMx chipCancer cell originIF panelcirculating tumor cellsimmunofluorescence stainingmicrofluidic chipsupported lipid bilayer

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Area of Science:

  • Oncology
  • Biomarker Discovery
  • Microfluidics

Background:

  • Circulating tumor cells (CTCs) are established biomarkers for cancer prognosis.
  • Current CTC analysis lacks the ability to determine the primary cancer origin.
  • Identifying CTC origin is crucial for effective cancer diagnosis and treatment.

Purpose of the Study:

  • To develop and validate a method for identifying the primary cancer source of CTCs.
  • To establish the sensitivity and specificity of the CMx platform and immunofluorescence panel for CTC origin determination.
  • To analyze CTCs in patient blood samples to confirm the method's clinical applicability.

Main Methods:

  • Utilized CMx microfluidic chips with anti-EpCAM-conjugated lipid bilayers for CTC capture.
  • Developed a 6-group immunofluorescence (IF) staining panel targeting specific cancer markers (panCK, CK18, CK7, TTF-1, CK20/CDX2, PSA/PSMA).
  • Validated the platform and panel using cancer cell lines and spiking experiments in blood samples from lung, colorectal, and prostate cancer patients and healthy individuals.

Main Results:

  • The CMx platform successfully enumerated lung, colorectal, and prostate cancer cells.
  • panCK(+) and CK18(+) CTCs were detected in all tested cancer types.
  • CK7/TTF-1, CK20/CDX2, and PSA/PSMA expression in CTCs accurately corresponded to lung, colorectal, and prostate cancer origins, respectively.
  • The IF panel demonstrated specificity in identifying the origin of CTCs in patient blood samples.

Conclusions:

  • An immunofluorescence staining panel was successfully designed to identify CTCs in peripheral blood.
  • This panel can correctly identify the primary cancer origin of detected CTCs.
  • The developed method offers a novel approach for non-invasive cancer diagnostics and origin determination.