title: Bone marrow stromal antigen 2 expressed in cancer cells promotes mammary tumor growth and metastasis.
abstract: BACKGROUND
  Several 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.
  
  
  METHODS
  Meta-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.
  
  
  RESULTS
  BST-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.
  
  
  CONCLUSIONS
  BST-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.
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, 51 Newton Road, Iowa City, IA, 52242-1109, USA. wadiedaniel-mahauadfernandez@uiowa.edu.|Interdisciplinary Graduate Program in Molecular and Cellular Biology (MCB), University of Iowa, 500 Newton Road, Iowa City, IA, 52242-1109, USA. wadiedaniel-mahauadfernandez@uiowa.edu.
authors.forename: Wadie D
authors.initials: WD
authors.lastname: Mahauad-Fernandez
authors.affiliation: Interdisciplinary Graduate Program in Molecular and Cellular Biology (MCB), University of Iowa, 500 Newton Road, Iowa City, IA, 52242-1109, USA. kris-demali@uiowa.edu.|Department of Biochemistry, Carver College of Medicine, University of Iowa, 51 Newton Road, Iowa City, IA, 52242-1109, USA. kris-demali@uiowa.edu.
authors.forename: Kris A
authors.initials: KA
authors.lastname: DeMali
authors.affiliation: Department of Pathology, Carver College of Medicine, University of Iowa, 51 Newton Road, Iowa City, IA, 52242-1109, USA. aolivier@cvm.msstate.edu.|Department of Pathobiology and Population Medicine, College of Veterinary Medicine, Mississippi State University, 240 Wise Center Drive, Starkville, MS, 39762-6100, USA. aolivier@cvm.msstate.edu.
authors.forename: Alicia K
authors.initials: AK
authors.lastname: Olivier
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, 51 Newton Road, Iowa City, IA, 52242-1109, USA. chioma-okeoma@uiowa.edu.|Interdisciplinary Graduate Program in Molecular and Cellular Biology (MCB), University of Iowa, 500 Newton Road, Iowa City, IA, 52242-1109, USA. chioma-okeoma@uiowa.edu.
authors.forename: Chioma M
authors.initials: CM
authors.lastname: Okeoma
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D016208:Databases, Factual; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism*; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C513868:BST2 protein, mouse