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

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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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Abbreviations

CRC:

Colon rectal cancers

CTCs:

Circulating tumor cells

CXCL1:

Chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha)

VEGF:

Vascular endothelial growth factor

TGF-beta:

Transforming growth factor beta

PAI-1:

Plasminogen activator inhibitor-1

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Conflict of interest

The authors declared that they have no competing interests.

Author information

Authors and Affiliations

  1. Clinical Pathology Laboratory, Department of Experimantal Oncology, National Cancer Institute, Istituto Tumori Giovanni Paolo II, Viale Orazio Flacco, 65, 70100, Bari, Italy

    Rosa Divella, Antonella Daniele, Ines Abbate, Antonia Bellizzi & Eufemia Savino

  2. Department of Pathology, National Cancer Institute Giovanni Paolo II, Viale Orazio Flacco 65, 70124, Bari, Italy

    Giovanni Simone & Grazia Giannone

  3. Medical Oncology Department, National Cancer Institute Giovanni Paolo II, Viale Orazio Flacco 65, 70124, Bari, Italy

    Francesco Giuliani

  4. Interventional Radiology and Medical Oncology Unit, National Cancer Institute Giovanni Paolo II, Viale Orazio Flacco 65, 70124, Bari, Italy

    Vito Fazio, Gennaro Gadaleta-Caldarola & Cosimo Damiano Gadaleta

  5. Interdisciplinary Department of Medicine, University of Bari School of Medicine, Piazza G. Cesare, 11, 70124, Bari, Italy

    Ivan Lolli, Carlo Sabbà & Antonio Mazzocca

  6. National Institute for Digestive Diseases, IRCCS “Saverio De Bellis”, Via Turi 27, 70013, Castellana Grotte, Bari, Italy

    Antonio Mazzocca

Authors
  1. Rosa Divella
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  2. Antonella Daniele
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  14. Antonio Mazzocca
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Corresponding authors

Correspondence to Rosa Divella or Antonio Mazzocca.

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Divella, R., Daniele, A., Abbate, I. et al. The presence of clustered circulating tumor cells (CTCs) and circulating cytokines define an aggressive phenotype in metastatic colorectal cancer. Cancer Causes Control 25, 1531–1541 (2014). https://doi.org/10.1007/s10552-014-0457-4

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  • DOI: https://doi.org/10.1007/s10552-014-0457-4

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