Abstract
Pinellia pedatisecta agglutinin (PPA) has previously been used in labeling fractions of myeloid leukemia cells in our laboratory. We report here that a bacterial expressed recombinant PPA domain b tagged with soluble coxsackie and adenovirus receptor (sCAR-PPAb) preferentially recognized drug resistant cancer cells K562/ADR and H460/5Fu, as compared to their parental cell lines. Pretreatment of K562/ADR cells with sCAR-PPAb significantly enhanced phagocytosis of K562/ADR by macrophages in vivo. Meanwhile, in a K562/ADR xenograft model, intratumoral injection of sCAR-PPAb induced macrophage infiltration and phagocytosis. Furthermore, immunoprecipitation, mass spectrometry and Western blot identified the membrane target of PPA on K562/ADR as sarcolemmal membrane associated protein (SLMAP). An antibody against SLMAP significantly promoted the phagocytosis of K562/ADR by macrophages in vitro. These findings suggest that PPA not only could be developed into a novel agent that can detect drug resistant cancer cells and predict chemotherapy outcome, but also it has potential value in immunotherapy against drug resistant cancer cells through inducing the tumoricidal activity of macrophages.
Highlights
Resistance to anticancer drugs is a major factor resulting in the failure of chemotherapy
Cells were treated with soluble coxsackie adenovirus receptor (sCAR)-PPAb combined with adenovirus Ad-EGFP followed by fluorescent microscope observation and flow cytometry analysis for portions of enhanced green fluorescent protein (EGFP) positive cells
The higher portion of EGFP positive K562/affinity to doxorubicin (ADR) cells was confirmed by a fluorescent microscope observation (Figure 1C), demonstrating a higher affinity of sCAR-PPAb to K562/ADR cells
Summary
Resistance to anticancer drugs is a major factor resulting in the failure of chemotherapy. P-glycoprotein and other ATP-binding cassette (ABC) family members catalyze the efflux of anticancer drugs thereby leading to drug resistance [1,2]. A minor population of cancer cells, named cancer stem cells, with the self-renewal capacity, expression of ABC family members, and resistance to apoptosis became a new factor responsible for MDR [3,4,5]. Niche microenvironment hosting cancer cells provides components which lead to insensitivity of cancer cells to anticancer drugs [6,7]. Glycosylation changes have been found to be correlated with MDR [8], providing a new feature for cancer drug resistance
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