Abstract
Cancer cells that transit from primary tumours into the circulatory system are known as circulating tumour cells (CTCs). These cancer cells have unique phenotypic and genotypic characteristics which allow them to survive within the circulation, subsequently extravasate and metastasise. CTCs have emerged as a useful diagnostic tool using “liquid biopsies” to report on the metastatic potential of cancers. However, CTCs by their nature interact with components of the blood circulatory system on a constant basis, influencing both their physical and morphological characteristics as well as metastatic capabilities. These properties and the associated molecular profile may provide critical diagnostic and prognostic capabilities in the clinic. Platelets interact with CTCs within minutes of their dissemination and are crucial in the formation of the initial metastatic niche. Platelets and coagulation proteins also alter the fate of a CTC by influencing EMT, promoting pro-survival signalling and aiding in evading immune cell destruction. CTCs have the capacity to directly hijack immune cells and utilise them to aid in CTC metastatic seeding processes. The disruption of CTC clusters may also offer a strategy for the treatment of advance staged cancers. Therapeutic disruption of these heterotypical interactions as well as direct CTC targeting hold great promise, especially with the advent of new immunotherapies and personalised medicines. Understanding the molecular role that platelets, immune cells and the coagulation cascade play in CTC biology will allow us to identify and characterise the most clinically relevant CTCs from patients. This will subsequently advance the clinical utility of CTCs in cancer diagnosis/prognosis.
Highlights
Metastatic progression is the most significant cause of cancer associated morbidity and mortality, causing over 8 million cancer deaths each year [1, 2]
Circulating tumour cells are critical components of the metastatic cascade that can be isolated from patients by a simple liquid biopsy, and can provide valuable information about the patient’s tumour profile and prognosis
The clinical utility of Circulating tumour tell (CTC) is yet to be fully recognised or appreciated, mainly because we only have a limited understanding of CTC biology
Summary
Metastatic progression is the most significant cause of cancer associated morbidity and mortality, causing over 8 million cancer deaths each year [1, 2]. The ‘seed and soil’ hypothesis put forward in 1889 describes cancer cells as “seeds” which must seek out the appropriate organ microenvironment or ‘soil’ that will support their sustained growth if they are to thrive [10, 11]. This hypothesis still remains a strong argument for the reasoning behind why certain tumour types have a tendency to metastasise to specific organs [5]. Identifying the molecular mechanisms involved in the initiation of haematogenous metastasis and the interactions with platelets, the coagulation cascade and immune cells could help us better understand specific outcomes in patients with metastatic disease. The overall aims of this review are to: 1. Outline the contribution of platelets, the coagulation cascade and immune cells on circulating tumour cells (CTCs) in metastasis
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