Characterization of CD45―/CD31+/CD105+ Circulating Cells in the Peripheral Blood of Patients with Gynecologic Malignancies

• Published in: Clinical cancer research Vol. 19; no. 19; pp. 5340 - 5350
• Main Authors: YU, Hyun-Kyung, LEE, Ho-Jeong, SUN JIN KIM, TAE JIN KIM, CHOI, Ha-Na, AHN, Jin-Hyung, CHOI, Ji-Young, SONG, Haeng-Seok, LEE, Ki-Heon, YEUP YOON, YI, Lee S. H, KIM, Jang-Seong
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.10.2013
• Subjects: Adult; Aged; Antigens, CD - metabolism; Antineoplastic agents; Biological and medical sciences; Biomarkers - metabolism; Endoglin; Endothelial Cells - metabolism; Female; Flow Cytometry; Genital Neoplasms, Female - blood; Genital Neoplasms, Female - metabolism; Genital Neoplasms, Female - pathology; Humans; Immunophenotyping; Leukocyte Common Antigens - metabolism; Leukocytes, Mononuclear - metabolism; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neovascularization, Pathologic - metabolism; Pharmacology. Drug treatments; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; Receptors, Cell Surface - metabolism; Tumors; Human; Biological fluid; Malignancy; Malignant tumor; In vitro; Blood; Cancer
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-12-3685

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. 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. 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. 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.