Monitoring of Serum Levels of Angiogenin, ENA-78 and GRO Chemokines in Patients with Renal Cell Carcinoma (RCC) in the Course of the Treatment

Dagmar Hlávková,Miroslav Podhola,Vladimíra Vroblová,Ctirad Andrýs,Otakar Kopecký,Doris Vokurková,Šárka Lukešová,Hynek Šafránek,Petr Morávek

doi:10.14712/18059694.2017.22

Dagmar Hlávková, Miroslav Podhola + Show 7 more

Open Access

https://doi.org/10.14712/18059694.2017.22

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Abstract

Tumour progression requires the presence of a rich vascular supply. A number of cytokines, chemokines and proteases participate in the process of tumour angiogenesis. We evaluated serum levels of angiogenin, panGRO (Growth Related Oncogene) (CXCL 1,2,3) and ENA-78 (Epithelial Neutrophil Activating) (CXCL5) in the serum of 32 patients with RCC (renal cell carcinoma) and 14 healthy blood donors by means of a protein array analysis. The patients were divided into three groups according to their disease stages (I+II, III, IV). We discovered significant differences between the blood donors and patients with RCC both in pre-operative and post-operative angiogenin, panGRO and ENA-78 levels. The increase in angiogenic factors lasted in patients even without metastases 2 months after surgery. We found no correlation between the levels of angiogenin and stages I+II, III and IV RCC. Patients with advanced carcinoma (stage III) had pre-operatively higher serum levels of ENA-78 than patients with stages I+II (p = 0,009) and IV (p< 0.001). Eight weeks after surgery the patients with stages I+II had significantly higher levels of panGRO than patients with stage IV.

Highlights

Neovascularization is important for the growth and development of metastases of solid tumours
Tumour-associated macrophages (TAMs) and dendritic cells (DCs) differentiate from circulating monocytes, which enter the tumorous tissue through the effect of chemo-attractive peptides and chemokines [13, 20]
Through the effect of angiogenic factors produced by tumorous cells, TAMs express VEGF-C (Vascular Endothelial Growth Factor), VEGF-D and VEGFR-3 (VEGF receptor), which participate in lymphangiogenesis and the distribution of metastases through lymphatic vessels

Summary

Introduction

Neovascularization is important for the growth and development of metastases of solid tumours. Tumour-associated macrophages (TAMs) and dendritic cells (DCs) differentiate from circulating monocytes, which enter the tumorous tissue through the effect of chemo-attractive peptides and chemokines (mainly CXCL1–3) [13, 20] These cells are the most effective antigen-presenting cells producing proinflammatory cytokines TNFα (Tumor Necrosis Factor), IL-1. Through the effect of angiogenic factors produced by tumorous cells, TAMs express VEGF-C (Vascular Endothelial Growth Factor), VEGF-D and VEGFR-3 (VEGF receptor), which participate in lymphangiogenesis and the distribution of metastases through lymphatic vessels. Both TAMs and tumour cells produce IL-10 which effectively blunts a cytotoxic T lymphocyte response to tumour antigens [10].

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