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Cancer Causes & Control
Published in: Cancer Causes & Control 11/2014

01-11-2014 | Original paper

The presence of clustered circulating tumor cells (CTCs) and circulating cytokines define an aggressive phenotype in metastatic colorectal cancer

Authors: Rosa Divella, Antonella Daniele, Ines Abbate, Antonia Bellizzi, Eufemia Savino, Giovanni Simone, Grazia Giannone, Francesco Giuliani, Vito Fazio, Gennaro Gadaleta-Caldarola, Cosimo Damiano Gadaleta, Ivan Lolli, Carlo Sabbà, Antonio Mazzocca

Published in: Cancer Causes & Control | Issue 11/2014

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Abstract

Purpose

Colon carcinoma is a malignant tumor showing a marked preference to metastasize to distant organs. The presence of circulating tumor cells (CTCs) in the peripheral blood is a prerequisite for the formation of distant metastases. However, whether circulating cytokines are linked to the circulation of tumor cells, as individual cells or clusters, remain unclear. In this study, we investigated the circulating levels of TGF-beta, CXCL1, VEGF and PAI-1 as potential bioindicators of the presence of CTCs in patients with metastatic colon cancer.

Methods

Circulating tumor cells (CTCs) were isolated from peripheral blood by immunomagnetic separation and phenotypically characterized in a cohort of 103 patients with metastatic colon cancer. TGF-beta, CXCL1, VEGF and PAI-1 concentrations were determined by immunoassay in plasma samples from the same patients.

Results

We detected two different populations of CTCs, single cells or clusters in patients with metastatic colon cancer. Importantly, we found that the presence of clustered CTCs is significantly associated with elevated circulating levels of TGF-beta and CXCL1 and with reduced overall survival. Finally, we observed that circulating levels of cytokines are differently associated with the two populations of CTCs.

Conclusions

Taken together, these findings show that detection of clustered CTCs represents a negative prognostic factor in patients with metastatic colon cancer. The presence of clustered CTCs is associated with elevated circulating levels of cytokines such as TGF-beta and CXCL1. This suggests an additional role for circulating cytokines as predictive tool for cancer prognosis and diagnosis of minimal residual disease as well as assessment of tumor sensitivity to anticancer therapy.
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Metadata
Title
The presence of clustered circulating tumor cells (CTCs) and circulating cytokines define an aggressive phenotype in metastatic colorectal cancer
Authors
Rosa Divella
Antonella Daniele
Ines Abbate
Antonia Bellizzi
Eufemia Savino
Giovanni Simone
Grazia Giannone
Francesco Giuliani
Vito Fazio
Gennaro Gadaleta-Caldarola
Cosimo Damiano Gadaleta
Ivan Lolli
Carlo Sabbà
Antonio Mazzocca
Publication date
01-11-2014
Publisher
Springer International Publishing
Published in
Cancer Causes & Control / Issue 11/2014
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-014-0457-4

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