Abstract
IntroductionSeveral innate immunity genes are overexpressed in human cancers and their roles remain controversial. Bone marrow stromal antigen 2 (BST-2) is one such gene whose role in cancer is not clear. BST-2 is a unique innate immunity gene with both antiviral and pro-tumor functions and therefore can serve as a paradigm for understanding the roles of other innate immunity genes in cancers.MethodsMeta-analysis of tumors from breast cancer patients obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets were evaluated for levels of BST-2 expression and for tumor aggressiveness. In vivo, we examined the effect of knockdown of BST-2 in two different murine carcinoma cells on tumor growth, metastasis, and survival. In vitro, we assessed the effect of carcinoma cell BST-2 knockdown and/or overexpression on adhesion, anchorage-independent growth, migration, and invasion.ResultsBST-2 in breast tumors and mammary cancer cells is a strong predictor of tumor size, tumor aggressiveness, and host survival. In humans, BST-2 mRNA is elevated in metastatic and invasive breast tumors. In mice, orthotopic implantation of mammary tumor cells lacking BST-2 increased tumor latency, decreased primary tumor growth, reduced metastases to distal organs, and prolonged host survival. Furthermore, we found that the cellular basis for the role of BST-2 in promoting tumorigenesis include BST-2-directed enhancement in cancer cell adhesion, anchorage-independency, migration, and invasion.ConclusionsBST-2 contributes to the emergence of neoplasia and malignant progression of breast cancer. Thus, BST-2 may (1) serve as a biomarker for aggressive breast cancers, and (2) be a novel target for breast cancer therapeutics.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-014-0493-8) contains supplementary material, which is available to authorized users.
Highlights
Several innate immunity genes are overexpressed in human cancers and their roles remain controversial
Bone marrow stromal antigen 2 (BST-2) expression in breast tumor is associated with tumor size, tumor aggressiveness, and host survival We studied BST-2 expression in different human breast cancer cells compared to normal mammary epithelial cells
Meta-analysis of large-scale human breast cancer data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) was used to assess the level of BST-2 mRNA in breast tumors
Summary
Several innate immunity genes are overexpressed in human cancers and their roles remain controversial. The oncogenesis of breast cancer involves multiple events, including genetic and epigenetic alterations in the behavior of normal and malignant cells, as well as other cells that interact with cancer cells [1] Such alterations modulate the functions of key host genes, which in turn affect cancer cell behavior including self-sufficiency in growth signals, adhesion, invasion, motility, and survival. Our understanding of specific genes linked to the development and progression of mammary cancer is unraveling These genes have enabled the development of targeted therapeutics. It has been shown that the innate immunity gene called bone marrow stromal antigen 2 (BST-2), known as tetherin, CD317, and HM1.24 is overexpressed in several cancers [4,5,6,7,8,9,10,11]. BST-2-mediated NF-кB activation occurs through the YXY motif on the cytoplasmic domain
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