title: hHSS1: a novel secreted factor and suppressor of glioma growth located at chromosome 19q13.33.
abstract: The completion of the Human Genome Project resulted in discovery of many unknown novel genes. This feat paved the way for the future development of novel therapeutics for the treatment of human disease based on novel biological functions and pathways. Towards this aim, we undertook a bioinformatics analysis of in-house microarray data derived from purified hematopoietic stem cell populations. This effort led to the discovery of HSS1 (Hematopoietic Signal peptide-containing Secreted 1) and its splice variant HSM1 (Hematopoietic Signal peptide-containing Membrane domain-containing 1). HSS1 gene is evolutionarily conserved across species, phyla and even kingdoms, including mammals, invertebrates and plants. Structural analysis showed no homology between HSS1 and known proteins or known protein domains, indicating that it was a truly novel protein. Interestingly, the human HSS1 (hHSS1) gene is located at chromosome 19q13.33, a genomic region implicated in various cancers, including malignant glioma. Stable expression of hHSS1 in glioma-derived A172 and U87 cell lines greatly reduced their proliferation rates compared to mock-transfected cells. hHSS1 expression significantly affected the malignant phenotype of U87 cells both in vitro and in vivo. Further, preliminary immunohistochemical analysis revealed an increase in hHSS1/HSM1 immunoreactivity in two out of four high-grade astrocytomas (glioblastoma multiforme, WHO IV) as compared to low expression in all four low-grade diffuse astrocytomas (WHO grade II). High-expression of hHSS1 in high-grade gliomas was further supported by microarray data, which indicated that mesenchymal subclass gliomas exclusively up-regulated hHSS1. Our data reveal that HSS1 is a truly novel protein defining a new class of secreted factors, and that it may have an important role in cancer, particularly glioma.
authors.affiliation: Neumedicines Inc, 133 N Altadena Dr. #310, Pasadena, CA 91107, USA.
authors.forename: Katiana S
authors.initials: KS
authors.lastname: Junes-Gill
authors.forename: Timothy K
authors.initials: TK
authors.lastname: Gallaher
authors.forename: Zoya
authors.initials: Z
authors.lastname: Gluzman-Poltorak
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Miller
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Wheeler
authors.forename: Xuemo
authors.initials: X
authors.lastname: Fan
authors.forename: Lena A
authors.initials: LA
authors.lastname: Basile
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D003001:Cloning, Molecular; D020869:Gene Expression Profiling; D015723:Gene Library; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology*; D006031:Glycosylation; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; C543592:EMC10 protein, human; C559277:HSS1 protein, mouse; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins