Circulating tumor cell clusters: What we know and what we expect (Review)

Abstract

The major cause of cancer-associated mortality is tumor metastasis, a disease that is far from understood. Many studies have observed circulating tumor cells (CTCs) in patients' circulation systems, and a few latest investigations showed that CTC clusters have a potentially high capacity of metastasis. The capture and analysis of CTC clusters offer new insights into tumor metastasis and can facilitate the development of cancer treatments. We reviewed the research history of the CTC clusters, as well as the technologies used for detecting and isolating CTC clusters. In addition, we discuss the characteristics of CTC clusters and their roles in tumor dissemination. Clinical relevance of CTC clusters was also implicated in currently limited data. Moving forward, the next frontier in this field is to develop more efficient capture methods and decipher conundrums of characterization of CTC clusters. This will ultimately identify the clinical value of CTC clusters as a biomarker and therapeutic target.

Figure 1

The milestones of CTC cluster discovery and isolation.

Figure 2

The CTC clusters merit higher potential of metastasis. In the circulation system, the hypoxic microenvironment of CTC cluster comprises of CTC cells, mesenchymal cells, epithelial cells, pericytes, immune cells, platelets, and cancer-associated fibroblasts would have some interactions with cytokines and exosomes. Such microenvironment protects CTC clusters from blood shear force damage and immune attack.