Document Type : Original Article
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
Angiogenesis, the process of formation of new blood vessels, is essential for development of solid tumors. At first, it was first assumed that angiogenesis is not implicated in the development of acute myeloid leukemia (AML) as a liquid tumor. One of the most important elements in bone marrow microenvironment is mesenchymal stem cells (MSCs). These cells possess an intrinsic tropism for sites of tumor in various types of cancers and have an impact on solid tumors growth by affecting the angiogenic process. But so far, our knowledge is limited about MSCs’ role in liquid tumors angiogenesis. By increasing our knowledge about the role of MSCs on angiogenesis, new therapeutic strategies can be used to improve the status of patients with leukemia.
Materials and Methods
In this experimental study, HL-60, K562 and U937 cells were separately co-cultured with bone marrow derived-MSCs and after 8, 16 and 24 hours, alterations in the expression of 10 chemokine genes involved in angiogenesis, were evaluated by quantitative real time-polymerase chain reaction (qRT-PCR). Mono-cultures of leukemia cell lines were used as controls.
We observed that in HL-60 and K562 cells co-cultured with MSCs, the expression of CXCL10 and CXCL3 genes are increased, respectively as compared to the control cells. Also, in U937 cells co-cultured with MSCs, the expression of CXCL6 gene was upgraded. Moreover in U937 cells, CCL2 gene expression in the first 16 hours was lower than the control cells, while within 24 hours its expression augmented.
Our observations, for the first time, demonstrated that bone marrow (BM)-MSCs are able to alter the expression profile of chemokine genes involved in angiogenesis, in acute myeloid leukemia cell lines. MSCs cause different effects on angiogenesis in different leukemia cell lines; in some cases, MSCs promote angiogenesis, and in others, inhibit it.