Survival Mechanisms and Influence Factors of Circulating Tumor Cells.

Wen-Chao Wang,Jian Peng,Mou-Bin Lin,Le-Hua Shi,Xiao-Feng Zhang,Ai-Li Wang,Ya-Qin Bie,Xi-Feng Li

doi:10.1155/2018/6304701

Wen-Chao Wang, Jian Peng + Show 6 more

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https://doi.org/10.1155/2018/6304701

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Abstract

Circulating tumor cells (CTCs) are cancer cells shed from either the primary tumor or its metastases that circulate in the peripheral blood. The CTCs are regarded as the source of tumor recurrence and metastasis and speculated as the indicators of residual tumors, thereby indicating a poor prognosis. Although CTCs play a vital role in tumor metastasis and recurrence, little is known about the underlying survival mechanisms in the blood circulation. The accumulating evidence has revealed that CTCs might survive in the peripheral blood by overcoming the mechanical damage due to shear stress, resistance to anoikis, evasion of immune destruction, and resistance to chemotherapy. The present review addresses the putative survival mechanisms underlying the formation and migration of CTCs according to their biological characteristics and blood microenvironment. In addition, the relationship between CTCs and microenvironment is illustrated, and the influencing factors related to the interactions of CTCs with various components in the peripheral blood are reviewed with respect to the platelets, immune cells, cytokines, and circulating tumor microemboli (CTM). Furthermore, the recent advances in the new treatment strategies targeting the survival mechanisms of CTCs are also discussed.

Highlights

Recurrence or metastasis is the major cause of poor prognosis and mortality in patients with malignant tumor, >90% of cancer-associated deaths are caused by metastasis, and micrometastasis is the early event in the process of tumor metastasis [1, 2]
The results indicated the proneness of these patients to develop metastasis/recurrence than those with CD44 (-) Circulating tumor cells (CTCs), thereby indicating that the circulating tumor stem cells (CTSCs) might provide a clinically valuable prognosis than only CTCs [31]
The results showed Ki67 expression was detected in individual CTCs from blood specimens (n=20) in variable proportions of cells, which present a sharp contrast with all circulating tumor microemboli (CTM) (n=34) were negative expression for Ki67, even in patients with Ki67 (+) CTCs [35]

Summary

Introduction

Recurrence or metastasis is the major cause of poor prognosis and mortality in patients with malignant tumor, >90% of cancer-associated deaths are caused by metastasis, and micrometastasis is the early event in the process of tumor metastasis [1, 2]. As a highly heterogeneous cell population, CTCs migrate away from a primary/metastasis tumor via the blood circulation to form secondary tumors in distant organs. They are considered as tumor micrometastasis biomarkers and real-time “liquid biopsy” sample, and the analysis of CTCs requires a blood sample that might provide an easy-to-repeat approach. In recent years, accumulating studies focused on the survival mechanisms of the formation and migration process of CTCs based on their biological characteristics and blood microenvironment (see Figure 1); the effects on the mechanism of resistance to anoikis and evasion from immune destruction were emphasized. Various components in the peripheral blood, such as platelets, immune cells, cytokines, and CTMs, may interact with CTCs and promote their survival

Biology of CTCs

Survival Mechanisms of CTCs in Blood Microenvironment

New Treatment Strategies Targeting the Survival Mechanisms of CTCs

Findings

Conclusions