The presence of clustered circulating tumor cells (CTCs) and circulating cytokines define an aggressive phenotype in metastatic colorectal cancer
The presence of clustered circulating tumor cells (CTCs) and circulating cytokines define an aggressive phenotype in metastatic colorectal cancer
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DOI：
10.1007/s10552-014-0457-4
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发表时间：
2014-11-01
影响因子：
2.3
通讯作者：
Mazzocca, Antonio
中科院分区：
文献类型：
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作者：
Divella, Rosa;Daniele, Antonella;Mazzocca, Antonio
结肠癌是一种明显倾向于转移到远处器官的恶性肿瘤。外周血中循环肿瘤细胞（CTCs）的存在是远处转移形成的先决条件。然而，循环细胞因子是否与肿瘤细胞的循环有关，作为单个细胞还是集群，尚不清楚。在这项研究中，我们研究了tgf - β、CXCL1、VEGF和PAI-1的循环水平作为转移性结肠癌患者ctc存在的潜在生物指标。通过免疫磁分离从外周血中分离出循环肿瘤细胞（CTCs），并对103例转移性结肠癌患者进行了表型表征。采用免疫分析法测定同一患者血浆样品中tgf - β、CXCL1、VEGF和PAI-1的浓度。我们在转移性结肠癌患者中检测到两种不同的ctc群体，单细胞或群集。重要的是，我们发现聚集性ctc的存在与tgf - β和CXCL1循环水平升高以及总生存率降低显著相关。最后，我们观察到循环细胞因子水平与两种ctc人群的相关性不同。综上所述，这些发现表明，在转移性结肠癌患者中，聚集性ctc的检测是一个负面的预后因素。聚集性ctc的存在与循环细胞因子（如tgf - β和CXCL1）水平升高有关。这表明循环细胞因子作为癌症预后和微小残留疾病诊断以及肿瘤对抗癌治疗敏感性评估的预测工具具有额外的作用。
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.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.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.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.