Abstract 3672: Expression patterns of scavenger receptor B-1 (SR-B1) to guide biomimetic HDL gold nanoparticle therapy

Abstract

Abstract Introduction: Treatment options for many advanced cancers are fairly limited. New therapies that can open new paradigm are urgently needed. We have recently developed a novel synthetic biomimetic HDL gold nanoparticle (HDL NP) that demonstrated anti-tumor activity in cancer cells via apoptosis (Yang et al. PNAS, 2013) Its activity correlated with the expression of scavenger receptor-B1 (SR-B1) that binds to natural HDLs and HDL NPs. SR-B1 is a high-affinity HDL receptor that facilitates the bidirectional flux of free cholesterol and the transport of esterified cholesterol to cells. The mechanism of action of HDL NPs involved alterations in cholesterol flux and metabolism as well as cholesterol-based cell-signaling pathways. Understanding the expression patterns of SR-B1 in various human cancers can assist in developing HDL NP therapy to broader indications. Methods: We used Oncomine Research Edition public database to assess the gene expression levels of SR-B1 in various human cell lines, cancer tissues, and normal tissues. T test was use to compare cell line with the highest SR-B1 expression with the rest of cell lines of various tumor types. Also comparison was made between resected human cancer tissues and their counterpart normal tissues across various histologies. Each significant t test results from all publicly available array datasets within Oncomine were counted and compared among different tumor types. Results: First, we compared the mRNA levels of SR-B1 in human cancer tissues with those of normal tissues. Twenty different tumor types were included. Among 20 different datasets of renal cell carcinoma, 12 (60%) revealed statistically significant increase in SR-B1 expression in cancer compared with normal renal tissue samples. Other tumor types that showed ≥10% of databsets demonstrating the same pattern of expression were esophageal (44%, 4/9), melanoma (43%, 3/7), gastric (26%, 6/23), leukemia (21%, 6/29), lymphoma (20%, 6/30), colorectal (19%, 7/36), liver (15%, 2/13), and prostate cancer (15%, 3/20). Second, we compared the mRNA levels of SR-B1 across various human cancer cell lines. Among 17 different datasets that contain cancer cell lines including melanoma cell lines, melanoma was found to have the highest level of SR-B1 expression compared with the rest of the cell lines of various cancer types in 11 (65%) datasets. Other tumor types associated with ≥10% of datasets demonstrating the same highest level of SR-B1 expression were liver (33%, 4/12), kidney (12%, 2/17), and leukemia (11%, 2/19). Discussion: We found that renal cell carcinoma, melanoma, and hepatocellular carcinoma were among the cancers that expressed higher levels of SR-B1 compared with other cancers as well as with their normal tissues. These tumors merit further investigation as targets for HDL NP therapy either in the form of mono-therapy or in combination. Citation Format: Young Kwang Chae, Alan Pan, Denise Scholtens, Shuo Yang, Jonathan Rink, Colby S. Thaxton, Leo Gordon. Expression patterns of scavenger receptor B-1 (SR-B1) to guide biomimetic HDL gold nanoparticle therapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3672. doi:10.1158/1538-7445.AM2015-3672