鉴定妇科恶性肿瘤患者外周血中 CD45-/CD31+/CD105+ 循环细胞的特征。

Characterization of CD45-/CD31+/CD105+ circulating cells in the peripheral blood of patients with gynecologic malignancies.

机构信息

Authors' Affiliations: Mogam Biotechnology Research Institute, Yongin; Department of Biological Science, Sungkyunkwan University, Suwon; Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine, Seoul; Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea; and Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

出版信息

Clin Cancer Res. 2013 Oct 1;19(19):5340-50. doi: 10.1158/1078-0432.CCR-12-3685. Epub 2013 Aug 6.

DOI:10.1158/1078-0432.CCR-12-3685

PMID:23922300

Abstract

PURPOSE

Circulating endothelial cells (CEC) have been widely used as a prognostic biomarker and regarded as a promising strategy for monitoring the response to treatment in several cancers. However, the presence and biologic roles of CECs have remained controversial for decades because technical standards for the identification and quantification of CECs have not been established. Here, we hypothesized that CECs detected by flow cytometry might be monocytes rather than endothelial cells.

EXPERIMENTAL DESIGN

The frequency of representative CEC subsets (i.e., CD45(-)/CD31(+), CD45(-)/CD31(+)/CD146(+), CD45(-)/CD31(+)/CD105(+)) was analyzed in the peripheral blood of patients with gynecologic cancer (n = 56) and healthy volunteers (n = 44). CD45(-)/CD31(+) cells, which are components of CECs, were isolated and the expression of various markers (CD146, CD105, vWF, and CD144 for endothelial cells; CD68 and CD14 for monocytes) was examined by immunocytochemistry.

RESULTS

CD45(-)/CD31(+)/CD105(+) cells were significantly increased in the peripheral blood of patients with cancer, whereas evaluation of CD45(-)/CD31(+)/CD146(+) cells was not possible both in patients with cancer and healthy controls due to the limited resolution of the flow cytometry. Immunocytochemistry analyses showed that these CD45(-)/CD31(+)/CD105(+) cells did not express vWF and CD146 but rather CD144. Furthermore, CD45(-)/CD31(+)/CD105(+) cells uniformly expressed the monocyte-specific markers CD14 and CD68. These results suggest that CD45(-)/CD31(+)/CD105(+) cells carry the characteristics of monocytes rather than endothelial cells.

CONCLUSIONS

Our data indicate that CD45(-)/CD31(+)/CD105(+) circulating cells, which are significantly increased in the peripheral blood of patients with gynecologic cancer, are monocytes rather than endothelial cells. Further investigation is required to determine the biologic significance of their presence and function in relation with angiogenesis.

摘要

目的

循环内皮细胞 (CEC) 已被广泛用作预后生物标志物，并被认为是监测几种癌症治疗反应的有前途的策略。然而，由于尚未建立 CEC 的鉴定和定量的技术标准，因此几十年来 CEC 的存在及其生物学作用一直存在争议。在这里，我们假设通过流式细胞术检测到的 CEC 可能是单核细胞而不是内皮细胞。

实验设计

分析了妇科癌症患者（n=56）和健康志愿者（n=44）外周血中代表性 CEC 亚群（即 CD45(-)/CD31(+)、CD45(-)/CD31(+)/CD146(+)、CD45(-)/CD31(+)/CD105(+)）的频率。分离 CD45(-)/CD31(+)细胞，并通过免疫细胞化学检查各种标记物（内皮细胞的 CD146、CD105、vWF 和 CD144；单核细胞的 CD68 和 CD14）的表达。

结果

癌症患者外周血中 CD45(-)/CD31(+)/CD105(+)细胞明显增加，而由于流式细胞术的分辨率有限，无法对癌症患者和健康对照者进行 CD45(-)/CD31(+)/CD146(+)细胞的评估。免疫细胞化学分析表明，这些 CD45(-)/CD31(+)/CD105(+)细胞不表达 vWF 和 CD146，而是表达 CD144。此外，CD45(-)/CD31(+)/CD105(+)细胞均表达单核细胞特异性标记物 CD14 和 CD68。这些结果表明，CD45(-)/CD31(+)/CD105(+)细胞具有单核细胞的特征，而不是内皮细胞的特征。