A functional interaction between the CCR5 and CD34 molecules expressed in hematopoietic cells can support (or even promote) the development of cancer

• Main Authors: Bruna Kulmann-Leal, Joel Henrique Ellwanger, José Artur Bogo Chies
• Format: Article
• Language: English
• Published: Elsevier 2020-01-01
• Series: Hematology, Transfusion and Cell Therapy
• Online Access: http://www.sciencedirect.com/science/article/pii/S253113791930166X

Inflammation and angiogenesis are linked to the development of cancer since both can support the establishment of a tumor-prone microenvironment. The CCR5 is a major regulatory molecule involved in inflammation. The CD34 molecule is commonly described as a hematopoietic stem cell marker, and CD34+ cells are involved in the regulation of distinct physiological processes, including angiogenesis. CCR5 participates in the development of various types of cancer, and recently, a reduced CCR5 expression was associated with low CD34+ cell counts in human cord blood. A naturally occurring genetic variant of the CCR5 gene, the so-called CCR5Δ32 polymorphism, consists of a 32 base-pair deletion in the DNA, interfering in the CCR5 protein levels on the cell surface. When in homozygosis, this variant leads to a total absence of CCR5 expression on the cell surface. In heterozygous individuals, CCR5 surface levels are reduced. Based on these key findings, we hypothesize that a functional interaction can connect CCR5 and CD34 molecules (giving rise to a “CCR5-CD34 axis”). According to this, a CCR5-CD34 interaction can potentially support the development of different types of cancer. Consequently, the lack of CCR5 in association with reduced CD34+ cell counts could indicate a protective factor against the development of cancer. It is required to characterize in detail the functional relationship between CCR5 and CD34 proteins, as well as the real influence of both molecules on the susceptibility and development of cancer at population level. If our hypothesis is confirmed, the CCR5-CD34 axis may be a potential target in the development of anti-cancer therapies. Keywords: CC chemokine receptor 5, CCR5Δ32, CD34, Cancer, Angiogenesis, Tumorigenesis, Inflammation