Chapter 111 : Circulating Tumor Cells as an Analytical Tool in the Management of Patients with Cancer

Abstract:

Circulating tumor cells (CTC), first described in 1869 as cells in the blood identical to those of the cancer itself (1), originate from the primary tumor or metastatic deposits after intravasation through the tumor vasculature by mechanisms that are not completely understood (Fig. 1) (2). Although most CTC die in the circulation, a proportion of them have the ability to spread, seed, and proliferate in distant sites to form secondary metastases (3) (estimated to be 0.05%) or to reestablish in the organ of origin to form new tumors (4), as demonstrated in short-term proliferation experiments (3, 5). First described by Paget in 1889, in his “seed and soil” hypothesis (6), the process of metastatic dissemination is driven by chemokines and integrins specific to the tumor type and by the adhesive interactions of the CTC with the vasculature and extracellular matrix components (4, 7–9). As an example, β4 integrin signaling promotes tumor cell adhesion to the endothelium through ErbB2-mediated vascular endothelial growth factor secretion and has been involved in metastatic development (10). Additionally, CTC have the ability to secrete stem cell-like factors to promote proliferation and self-renewal (11, 12). Microembolic clusters of CTC, isolated by a variety of techniques, are associated with a particularly poor prognosis, which may be related to the enhanced activation of survival pathways by cellular contact and to mechanical capture in the microvasculature, further enabling metastasis formation (13, 14).