Abstract A12: Establishment of myeloid lineage cell line that resembles myeloid-derived suppressive cells

Myeloid-derived suppressive cells (MDSCs) are inflammatory cells that play critical roles in promoting cancer growth and metastasis. In order to facilitate characterization of biochemical and cellular mechanisms of MDSCs, it is urgent to establish an "MDSC-like" cell line for pharmacological and immunotherapeutic applications. Lysosomal acid lipase (LAL) is a critical lipid enzyme in the metabolic signaling pathway that hydrolyzes cholesteryl esters (CE) and triglycerides (TG) in lysosomes. In mice, lack of LAL in genetically ablated knockout mice (lal-/-) shows systemic expansion of MDSCs, which directly stimulate cancer cell proliferation, and suppress T cell proliferation and impair T cell function. The Affymetrix Genechip microarray assay reveals over-activation of the mTOR signaling pathway in lal-/- MDSCs. By cross breeding of immortomouse (simian virus 40 large T antigen transgenic mice) with wild type and lal-/- mice, we have established wild type (HD1A) and lal-/- (HD1B) myeloid cell lines. Compared with HD1A cells, HD1B cells demonstrated many characteristics similar to lal-/- MDSCs. HD1B cells exhibited increased lysosomes around perinuclear areas. HD1B cells showed increased glycolytic metabolism during blockage of fatty acid metabolism to fuel the energy need. Compared with HD1A cells, HD1B cells showed increased glucose concentration, suggesting the enhanced glycolytic metabolic pathway, in which glucose converts into pyruvate. Indeed, the pyruvate concentration...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Cancer Metabolic Pathways: Poster Presentations - Proffered Abstracts Source Type: research