The viable circulating tumor cells with cancer stem cells feature, where is the way out?

Abstract

With cancer stem cells (CSCs) became the research hotspot, emerging studies attempt to reveal the functions of these special subsets in tumorigenesis. Although various approaches have been used in CSCs researches, only a few could really reflect or simulate the microenvironment in vivo. At present, CSCs theories are still difficult to apply for clinical remedy because CSCs subpopulations are always hard to identify and trace. Thus an ideal approach for clinicians and researchers is urgently needed. Circulating tumor cells (CTCs), as the method of noninvasive-liquid biopsy, could be detected in the peripheral blood (PB) from many tumors and even could be treated as procurators for CSCs deeper researches from patient-derived sample. However, CTCs, as a diagnostic marker, also raise much controversy over theirs clinical value. Mechanisms causing CTCs to shed from the tumor have not been fully characterized, thus it is unclear whether CTCs represent the entire makeup of cancer cells in the tumor or only a subset. The heterogeneity of CTCs also caused different clinical outcomes. To overcome these unsolved problems, recently, CTC researches are not just depend on enumerations, whereas those CTC subsets that could expand in vitro may play a pivotal role in the metastatic cascade. Here, we retrospect the CTC developmental history and discourse upon the enrichment of viable CTCs in functional assays, probe the further avenue at the crossroad.

Keywords: Circulating tumor cells; Culture; Expansion; Function.

Fig. 1

CTC researches undergone the three stages CTC enumerations include various subsets such as dormant cells, apoptotic cells, and even normal hemopoietic stem cells, only depend on enumeration is not suitable for clinical evaluation. Whereas, further the studies in molecular characterization by RNA or exon sequencing could explain CTC heterogeneity, expanded CTCs could be the special subsets not only for deeper molecular-level researches but for functional analyses and guide the clinical therapy

Fig. 2

The most influential events contributing to the causal relationship between CSCs and CTCs The fonts in black indicate events related to CSCs [, , , , , –68]. The fonts in blue indicate events related to CTCs [, , –, , , –78]. And recent years, many evidence showed the inextricable connection between CSCs and CTCs, the expanded CTCs subsets are always used as a tool to reflect intrinsic characteristic of CSCs [25, 77, 78]. The abbreviations in Fig. 2: stem cells (SCs); mesenchymal stem cells (MSCs); serum-free medium (SFM); disseminated tumor cells (DTC); CTC-derived xenografts (CDX) [–, –48, 51, 52, 54]