Detection of circulating tumor cells: Clinical relevance of a novel metastatic tumor marker

Abstract

Most cancer-related deaths are caused by the hematogenous spread of cancer cells to distant organs and their subsequent metastasis. During the early stages of the metastatic cascade, cancer cells disseminate from the primary site via the lymphatic vessels and/or by hematogenous routes. Circulating tumor cells (CTCs), cancer cells that have disseminated into the systemic circulation, may be a predictor of poor prognosis in several carcinomas. An understanding of the molecular mechanisms involved in the blood-borne dissemination of cancer cells may help to clarify the process of metastasis and provide a powerful and non-invasive approach for anticancer treatments that are tailored to individual patients.

Figure 1.

The process of CTC metastasis. Cancer cells with localized invasion require epithelial mesenchymal transition (EMT), by which adherent cancer cells achieve the ability to migrate, as well as with the loss of integrity of the basement membrane (BM) and the extracellular matrix (ECM). The process permits some metastatic cancer cells to intravasate into the blood. CTCs interact with the microenvironment in the circulation. Finally, only a small proportion of CTCs with the ability to metastasize, or those with traits similar to those of cancer stem cells, are thought to extravasate to distal organs and develop macrometastases. Genetic and molecular analysis of these rare cells may provide a novel tool for evaluating their biological and clinical relevance.

Figure 2.

Enrichment and identification of CTCs. CTCs were stained with (A) anti-cytokeratin 8/18/19-Alexa 488-positive, (B) anti-CD45-Alexa 594-negative, (C) 4,6-diamidino-2-phenylindole (DAPI)-positive antibodies. (D) Merged image of A, B and C; (E and G) CTCs re-stained with Hematoxylin and Eosin (H&E). (F and H) CTCs hybridized with DNA probes targeting specific chromosome 8 (green) and chromosome 20 (red), showing polysomy of chromosomes 8 and 20. Original magnification, ×100. Scale bar, 10 μm.