Abstract
A growing tumor is constantly secreting inflammatory chemokines and cytokines that induce release of immature myeloid cells, including myeloid-derived suppressor cells (MDSCs) and macrophages, from the bone marrow. These cells not only promote tumor growth, but also prepare distant organs for tumor metastasis. On the other hand, the myeloid-derived cells also have phagocytic potential, and can serve as vehicles for drug delivery. We have previously identified thioaptamers that bind a subset of MDSCs with high affinity and specificity. In the current study, we applied one of the thioaptamers as a probe to track myeloid cell distribution in the bone, liver, spleen and tumor in multiple murine models of breast cancer including the 4T1 syngeneic model and MDA-MB-231 and SUM159 xenograft models. Information generated from this study will facilitate further understanding of tumor growth and metastasis, and predict biodistribution patterns of cell-mediated drug delivery.
Highlights
A growing tumor is increasingly infiltrated with immature myeloid-derived suppressor cells (MDSCs) comprising polymorphonuclear MDSCs (PMN-MDSCs) and monocytic MDSCs (M-MDSCs), the latter can differentiate into tumor-associated macrophages (TAMs) in the inflammatory tissue [1,2].These tumor-associated myeloid cells produce high levels of reactive oxygen and nitrogen species, and anti-inflammatory cytokines, and are responsible for suppression of anti-tumor functions of other immune cells, including T and B lymphocytes and natural killer cells [3,4,5,6]
Our results showed that the T1 aptamer was able to recognize and bind onto granulocytes and some macrophages in different breast cancer models
Single cell suspensions from spleens were prepared by grinding the tissue through 40-μm nylon filters (BD Biosciences, San Jose, CA, USA), and bone marrow cells were harvested from the femur and tibia by flushing them with phosphate buffer saline (PBS)
Summary
A growing tumor is increasingly infiltrated with immature myeloid-derived suppressor cells (MDSCs) comprising polymorphonuclear MDSCs (PMN-MDSCs) and monocytic MDSCs (M-MDSCs), the latter can differentiate into tumor-associated macrophages (TAMs) in the inflammatory tissue [1,2]. The T1 aptamer, showed high binding affinity to the granulocytes/PMN-MDSCs and a selected number of tumor cells It was used as an affinity moiety for targeted drug delivery to primary breast cancer [11]. Our results showed that the T1 aptamer was able to recognize and bind onto granulocytes and some macrophages in different breast cancer models This T1 aptamer has shown a strong binding ability onto human bone marrow hematopoietic cells. Not restricted to murine cancer models, the T1 aptamer is a promising tool to target human cells, where there is a strong indication that the T1 aptamer can be applied in clinical use
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