Circulating tumor cells: a window into cancer biology and metastasis

Abstract

The presence of circulating tumor cells (CTCs) accompanies tumor invasion into the bloodstream. Detection, monitoring, and molecular analysis of these rare cancer cells shed into blood will provide a powerful and noninvasive approach for the detection of early disease, assessing prognosis and therapeutic response in established cancers, and targeting metastatic precursor cells. We review current and emerging technologies for CTC isolation, with a focus on capture efficiency, purity, and viability of CTCs, and their potential clinical applications.

Figure 1

Schematic representation of epithelial to mesenchymal transition (EMT), by which adherent epithelial cells are thought to acquire migratory cell fates, combined with the activation of proteases which compromise the integrity of the basement membrane (BM) and the extracellular matix (ECM), leading to intravasation of tumor cells into the bloodstream. The rare tumor cells that are present in the bloodstream, admixed with billions of normal blood cells, are defined as circulating tumor cells (CTC). A subset of CTCs are thought to extravasate at distal sites such as the lung, liver, bone and brain to establish metastatic lesions. Isolation, enumeration, and genetic and biomarker analysis of CTCs will provide insight into the biology of these putative metastatic precursors.