Chaves K C, Costa E M, Teixeira L F, Bellini M H
Department of Medicine, Nephrology Division, Federal University of São Paulo, São Paulo 04039-000, Brazil.
Biotechnology Department, Nuclear and Energy Research Institute, São Paulo 05508-000, Brazil.
Exp Oncol. 2018 Mar;40(1):24-32.
To evaluate the role of endostatin (ES) gene therapy on myeloid-derived suppressor cells (MDSC) in a metastatic model of renal cell carcinoma (RCC).
Balb/C mice bearing orthotopic Renca tumors were treated with NIH/3T3-LendSN or, as a control, with NIH/3T3-LXSN cells. At the end of in vivo experiment, plasma and tissue lung samples were collected. Plasma ES and granulocyte colony stimulating factor (G-CSF) levels were measured by ELISA and Milliplex, respectively. Quantification of CD11bGr-1 cells and their subsets was performed by flow cytometry. Reactive oxygen species (ROS) production was measured in CD11bGr-1 MDSC using the DCFDA marker by flow cytometry.
Metastatic RCC (mRCC) induced expansions of CD11bGr-1 MDSC and promoted accumulation of these cells and their subtypes in lymphoid organ and metastases. ES treatment promoted low G-CSF plasmatic levels which were produced by the tumor microenvironment, reflecting the reduced metastatic accumulation of CD11bGr-1 MDSC in the lungs. However, the therapy was selective for granulocytic cells, thus reducing the production of ROS.
These findings confirm the expansion of MDSC during metastatic progression of RCC and indicate the important role of ES in reducing MDSC and possible use of ES therapy in combined anticancer treatment.
