Pinellia pedatisecta agglutinin targets drug resistant K562/ADR leukemia cells through binding with sarcolemmal membrane associated protein and enhancing macrophage phagocytosis.
Where this comes from
- Record sourced from PubMed, PMID 24019967.
- Also identified by DOI 10.1371/journal.pone.0074363 and PMC identifier 3760846.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Pinelliapedatisecta 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.
Medical subject headings
- Agglutinins
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Macrophages
- Phagocytosis
- Pinellia
- Sarcolemma