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 language | English |
|---|---|
| Pages (from-to) | 1531-1541 |
| Number of pages | 11 |
| Journal | Cancer Causes and Control |
| Volume | 25 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Oct 31 2014 |
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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 journal › Article
}
TY - JOUR
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
Y1 - 2014/10/31
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.
KW - Cell clusters
KW - CTCs
KW - CXCL1
KW - Metastasis
KW - PAI-1
KW - TGF-beta
KW - VEGF
UR - http://www.scopus.com/inward/record.url?scp=84911975412&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84911975412&partnerID=8YFLogxK
U2 - 10.1007/s10552-014-0457-4
DO - 10.1007/s10552-014-0457-4
M3 - Article
C2 - 25135616
AN - SCOPUS:84911975412
VL - 25
SP - 1531
EP - 1541
JO - Cancer Causes and Control
JF - Cancer Causes and Control
SN - 0957-5243
IS - 11
ER -