Circulating tumor cell clusters: Insights into tumour dissemination and metastasis

ABSTRACT

Introduction: Metastasis results in more than 90% of cancer-related deaths globally. The process is thought to be facilitated by metastatic precursor cells, commonly termed circulating tumor cells (CTCs). CTCs can exist as single cells or cell clusters and travel through the lymphovasculature to distant organs where they can form overt metastasis.

Areas covered: Studies have highlighted that CTC clusters, which may be homotypic or heterotypic in composition, have a higher metastatic potential compared to single CTCs. The characterization of CTC clusters is becoming important as heterotypic clusters can provide a mechanism for immune evasion. This review summarizes the latest advances in CTC cluster-mediated metastasis and clinical significance.

Expert opinion: Comprehensive characterization of CTC clusters is needed to understand the cell types and interactions within clusters, in order to identify ways in which to reduce CTC cluster-mediated metastasis. The role of CTC clusters in prognosticating disease progression needs to be determined by documenting CTC clusters from the time of diagnosis over the course of therapy.

KEYWORDS:

• Circulating tumor cells
• CTC clusters
• homotypic
• heterotypic
• metastasis

Article highlights

• CTC clusters are more efficient at seeding metastasis than single CTCs

• CTC clusters have a higher metastatic capacity than single CTCs

• CTC clusters can be composed of only tumor cells (homotypic) or a milleiu of stromal, immune, and tumor cells (heterotypic)

• Heterotypic CTC clusters are able to evade the immune surveillance mechanisms

• CTC clusters are rare cells in the blood and advanced isolation and enrichment strategies are required for their capture

• Advances in microfluidic technologies have enabled the capture of CTC clusters

Acknowledgments

A Kulasinghe is supported by an NHMRC ECF fellowship (APP1157741) and Cure Cancer (APP1182179). K O’Byrne is supported by the Princess Alexandra Hospital Foundation grant.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.