Circulating Tumor Cells

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Presentation transcript:

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: visualization of an intact nucleus (using DAPI, 4′,6-diamidino-2-phenylindole, a DNA-binding fluorescent stain) expression of cytokeratin 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=ES0PVeYNpks

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/17314005 http://en.wikipedia.org/wiki/Circulating_tumor_cell http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0033788 http://www.genengnews.com/keywordsandtools/print/1/27863/