Diagnostic and prognostic relevance of microparticles in peripheral and uterine blood of patients with endometrial cancer
Abstract
Objectives: Exosomes — microvesicles which are secreted by living cells — can be produced from different cell types and detected in various body fluids. They are the carriers of intercellular information which regulate tumor microenvironment and are considered to be involved in tumor progression and metastasis. Cancer cells can secrete more exosomes than healthy cells, and are expected to be potential tools for tumor diagnosis and treatment.
Material and methods: In this report, we present the results of microparticle analysis in peripheral and uterine blood of patients with endometrial cancer. To the best of our knowledge, this study has been the first to report microvesicle status in peripheral and uterine blood samples. The aim of the study was to determine the amount of total (TF+), endothelial (CD144+) and monocytic (CD14+) microparticles. The counting of the selected microparticles in citrate plasma was performed using flow cytometry on the BD Canto II cytometer.
Results: We found that the total amount of microparticles in cancer patients was much higher than in healthy controls. Moreover, microparticle count in uterine blood was higher than in peripheral blood of patients with endometrial cancer. We
also demonstrated that the amount of microparticles correlates with the histologic grade and clinical stage of the tumor.
Conclusions: The most interesting finding in this work was the high level of TF, CD144 and CD14 MPs in uterine blood samples. Thus we can consider the monocyte-macrophage-derived MPs as a candidate marker of endometrial cancer and maybe very critical part of the endometrial carcinogenesis.
Keywords: endometrial cancerexosomesmicroparticlesbiomarkers
References
- Lemech CR, Ensell L, Paterson JC, et al. Enumeration and Molecular Characterisation of Circulating Tumour Cells in Endometrial Cancer. Oncology. 2016; 91(1): 48–54.
- Li XY, Wang X. The role of human cervical cancer oncogene in cancer progression. Int J Clin Exp Med. 2015; 8(6): 8363–8368.
- Colombo N, Creutzberg C, Amant F, et al. ESMO-ESGO-ESTRO Endometrial Consensus Conference Working Group. ESMO-ESGO-ESTRO consensus conference on endometrial cancer: Diagnosis, treatment and follow-up. Radiother Oncol. 2015; 117(3): 559–581.
- Kandoth C, Schultz N, Cherniack AD, et al. Cancer Genome Atlas Research Network; Integrated Genomic Characterization of Endometrial Carcinoma. Nature. 2013; 497: 67–73.
- Piulats JM, Guerra E, Gil-Martín M, et al. Molecular approaches for classifying endometrial carcinoma. Gynecol Oncol. 2017; 145(1): 200–207.
- Talhouk A, Hoang LN, McConechy MK, et al. Molecular classification of endometrial carcinoma on diagnostic specimens is highly concordant with final hysterectomy: Earlier prognostic information to guide treatment. Gynecol Oncol. 2016; 143(1): 46–53.
- van Niel G, D'Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 2018; 19(4): 213–228.
- Goon PKY, Lip GYH, Stonelake PS, et al. Circulating endothelial cells: markers of vascular dysfunction. Clin Lab. 2005; 51(9-10): 531–538.
- Kim CW, Lee HM, Lee TH, et al. Extracellular membrane vesicles from tumor cells promote angiogenesis via sphingomyelin. Cancer Res. 2002; 62(21): 6312–6317.
- Mancuso P, Calleri A, Cassi C, et al. Circulating endothelial cells as a novel marker of angiogenesis. Adv Exp Med Biol. 2003; 522: 83–97.
- Lin Y, Weisdorf DJ, Solovey A, et al. Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest. 2000; 105(1): 71–77.
- Ura B, Monasta L, Arrigoni G, et al. A proteomic approach for the identification of biomarkers in endometrial cancer uterine aspirate. Oncotarget. 2017; 8(65): 109536–109545.
- Gong J, Luk F, Jaiswal R, et al. Microparticles Mediate the Intercellular Regulation of microRNA-503 and Proline-Rich Tyrosine Kinase 2 to Alter the Migration and Invasion Capacity of Breast Cancer Cells. Front Oncol. 2014; 4: 220.
- Sun D, Zhuang X, Zhang S, et al. Exosomes are endogenous nanoparticles that can deliver biological information between cells. Adv Drug Deliv Rev. 2013; 65(3): 342–347.
- Jaiswal R, Gong J, Sambasivam S, et al. Microparticle-associated nucleic acids mediate trait dominance in cancer. FASEB J. 2012; 26(1): 420–429.
- Beerepoot LV, Mehra N, Vermaat JSP, et al. Increased levels of viable circulating endothelial cells are an indicator of progressive disease in cancer patients. Ann Oncol. 2004; 15(1): 139–145.
- Mancuso P, Burlini A, Pruneri G, et al. Resting and activated endothelial cells are increased in the peripheral blood of cancer patients. Blood. 2001; 97(11): 3658–3661.
