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

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

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1531-1541
Number of pages11
JournalCancer Causes and Control
Volume25
Issue number11
DOIs
Publication statusPublished - Oct 31 2014

Fingerprint

Circulating Neoplastic Cells
Colorectal Neoplasms
Cytokines
Phenotype
Transforming Growth Factor beta
Colonic Neoplasms
Plasminogen Activator Inhibitor 1
Vascular Endothelial Growth Factor A
Neoplasms
Immunomagnetic Separation
Residual Neoplasm
Immunoassay
Population
Colon
Neoplasm Metastasis
Carcinoma
Survival

Keywords

  • Cell clusters
  • CTCs
  • CXCL1
  • Metastasis
  • PAI-1
  • TGF-beta
  • VEGF

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

The presence of clustered circulating tumor cells (CTCs) and circulating cytokines define an aggressive phenotype in metastatic colorectal cancer. / Divella, Rosa; Daniele, Antonella; Abbate, Ines; Bellizzi, Antonia; Savino, Eufemia; Simone, Giovanni; Giannone, Grazia; Giuliani, Francesco; Fazio, Vito; Gadaleta-Caldarola, Gennaro; Gadaleta, Cosimo Damiano; Lolli, Ivan; Sabbà, Carlo; Mazzocca, Antonio.

In: Cancer Causes and Control, Vol. 25, No. 11, 31.10.2014, p. 1531-1541.

Research output: Contribution to journalArticle

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T1 - The presence of clustered circulating tumor cells (CTCs) and circulating cytokines define an aggressive phenotype in metastatic colorectal cancer

AU - Divella, Rosa

AU - Daniele, Antonella

AU - Abbate, Ines

AU - Bellizzi, Antonia

AU - Savino, Eufemia

AU - Simone, Giovanni

AU - Giannone, Grazia

AU - Giuliani, Francesco

AU - Fazio, Vito

AU - Gadaleta-Caldarola, Gennaro

AU - Gadaleta, Cosimo Damiano

AU - Lolli, Ivan

AU - Sabbà, Carlo

AU - Mazzocca, Antonio

PY - 2014/10/31

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N2 - 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.

AB - 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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