Previously, we reported apolipoprotein A-I (apoA-I), the major protein component of high-density lipoprotein (HDL), has potent anti-melanoma activity. We used DNA microarray and bioinformatics to interrogate gene expression profiles of tumors from apoA-I expressing (A-I Tg) versus apoA-I-null (A-I KO) animals to gain insights into mechanisms of apoA-I tumor protection. Differential expression analyses of 11 distinct tumors per group with > 1.
View Article and Find Full Text PDFApolipoprotein A-I (apoA-I) is the major protein constituent of high-density lipoprotein (HDL) and a target of myeloperoxidase-dependent oxidation in the artery wall. In atherosclerotic lesions, apoA-I exhibits marked oxidative modifications at multiple sites, including Trp Site-specific mutagenesis studies have suggested, but have not conclusively shown, that oxidative modification of Trp of apoA-I impairs many atheroprotective properties of this lipoprotein. Herein, we used genetic code expansion technology with an engineered tryptophanyl tRNA-synthetase (Trp-RS):suppressor tRNA pair to insert the noncanonical amino acid 5-hydroxytryptophan (5-OHTrp) at position 72 in recombinant human apoA-I and confirmed site-specific incorporation utilizing MS.
View Article and Find Full Text PDFIncreased circulating levels of apolipoprotein A-I (apoA-I), the major protein of high-density lipoprotein (HDL), by genetic manipulation or infusion, protects against melanoma growth and metastasis. Herein, we explored potential roles in melanoma tumorigenesis for host scavenger receptor class B, type 1 (SR-B1), and ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1), all mediators of apoA-I and HDL sterol and lipid transport function. In a syngeneic murine melanoma tumor model, B16F10, mice with global deletion of SR-B1 expression exhibited increased plasma HDL cholesterol (HDLc) levels and decreased tumor volume, indicating host SR-B1 does not directly contribute to HDL-associated anti-tumor activity.
View Article and Find Full Text PDFApolipoprotein A1 (apoA1) is the major protein component of high-density lipoprotein (HDL) and has well documented anti-inflammatory properties. To better understand the cellular and molecular basis of the anti-inflammatory actions of apoA1, we explored the effect of acute human apoA1 exposure on the migratory capacity of monocyte-derived cells in vitro and in vivo. Acute (20-60 min) apoA1 treatment induced a substantial (50-90%) reduction in macrophage chemotaxis to a range of chemoattractants.
View Article and Find Full Text PDFBackground: Renal cell carcinoma (RCC) patients treated with tyrosine kinase inhibitors (TKI) typically respond initially, but usually develop resistance to therapy. We utilised transcriptome analysis to identify gene expression changes during development of sunitinib resistance in a RCC patient-derived xenograft (PDX) model.
Methods: RCC tumours were harvested during pre-treatment, response and escape phases.