Circulating Tumor Cells
Circulating Tumor Cells (CTC)
• Metastasis: the spread of cancer from its
primary site to other places in the
body. Metastatic disease is the most common
cause of cancer-related death in patients with
solid tumors.
Metastasis Process
CTCs
• Standard definition of a CTC:
– Epithelial tumor cell which has adopted genetic
mutations that enable migration through the basement
membrane and the extracellular matrix, and is free to
circulate in the blood stream
– confirmed by:
1) visualization of an intact nucleus (using DAPI, 4′,6-diamidino-2phenylindole, a DNA-binding fluorescent stain)
2) expression of cytokeratin
3) lack of expression of the white blood cell marker, CD45, the
leukocyte-common antigen gene
- Invasive tumor cells tend to loose their epithelial antigens by the epithelial
to mesenchymal transition (EMT) process, so CTCs cannot be diagnosed
based on the expression of epithelial-specific transcripts or antigens
Clinical Usefulness
• Many metastatic lesions are never biopsied due
to anatomic inaccessibility and are unavailable for
biological characterization
• CTCs “liquid biopsy” - offer a readily accessible
means of studying the biology of metastatic cells
throughout the course of disease
– Could be used as an early cancer detection method as
well as monitoring for recurrence
• CTCs can be isolated and used to study the gene
variations commonly known to be associated
with cancer phenotypes
Detection in Blood
• Problems:
– Frequency is extremely
low
– 1-10 CTC per mL of whole
blood in patients with
metastatic disease
– 1 mL of blood contains
several million white
blood cells and a billion
red blood cells
Current Detection Methods
• Two main isolation techniques:
– biological properties - primarily based on antibody capturing methods
(affinity for EpCAM positive cells)
– physical properties - often filter-based, enabling the capture of CTCs by size.
• MagSweeper
– An automated device that uses a reiterative process of magnetic capture,
wash, and release to enrich CTCs, yielding a highly purified sample of live CTCs
that can be analyzed on a single-cell basis
• CellSearch system
– iron nano-particle coated with a polymer layer carrying biotin analogues and
conjugated with antibodies anti EpCAM for capturing CTCs; analyzer takes
images of isolated cell
• On-Q-ity platform
– Combines affinity capture with size filtration capture to isolate CTCs. About
100,000 micropillars, conjugated with antibody, line the chamber of the plastic
microfluidic device. The micropillars are arrayed in a gradient.
CTC Detection
• Video
• http://www.youtube.com/watch?v=ES0PVeYN
pks
• Learn more about current research into
isolating and studying CTCs!
• http://cancer.scripps.edu/research.aspx
• http://ctc-summit.com/
• http://www.ncbi.nlm.nih.gov/pubmed/17314
005
• http://en.wikipedia.org/wiki/Circulating_tumo
r_cell
• http://www.plosone.org/article/info%3Adoi%
2F10.1371%2Fjournal.pone.0033788
• http://www.genengnews.com/keywordsandto
ols/print/1/27863/