Top

Published in:

Open Access 01-04-2011 | Lab Investigation - Human/Animal Tissue

hHSS1: a novel secreted factor and suppressor of glioma growth located at chromosome 19q13.33

Authors: Katiana S. Junes-Gill, Timothy K. Gallaher, Zoya Gluzman-Poltorak, Joseph D. Miller, Christopher J. Wheeler, Xuemo Fan, Lena A. Basile

Published in: Journal of Neuro-Oncology | Issue 2/2011

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.

Venter JC, Adams MD, Myers EW et al (2001) The sequence of the human genome. Science 291:1304–1351PubMedCrossRef

Lander ES, Linton LM, Birren B et al (2001) Initial sequencing and analysis of the human genome. Nature 409:860–921PubMedCrossRef

Pawlowski K (2008) Uncharacterized/hypothetical proteins in biomedical ‘omics’ experiments: is novelty being swept under the carpet? Brief Funct Genomic Proteomic 7(4):283–290. doi:10.1093/bfgp/eln033 PubMedCrossRef

Zhong JF, Zhao Y, Sutton S et al (2005) Gene expression profile of murine long-term reconstituting vs. short-term reconstituting hematopoietic stem cells. PNAS 102:2448–2453PubMedCrossRef

Rubio M-P, Correa KM, Ueki K et al (1994) The putative glioma tumor suppressor gene on chromosome 19q maps between APOC2 and HRC ¹. Cancer Res 54:4760–4763PubMed

Smith JS, Tachibana I, Pohl U et al (2000) A transcript map of the chromosome 19q-arm glioma tumor suppressor region. Genomics 64(1):44–50PubMedCrossRef

Zhao Y, Lin Y, Zhan Y et al (2000) Hematopoietic stem cell characterization and its regulation in BM transplantation. Blood 96:3016–3022PubMed

Phillips HS, Kharbanda S, Chen R et al (2006) Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 9(3):157–173PubMedCrossRef

Kuhlman B, Dantas G, Ireton GC, Varani G, Stoddard BL, Baker D (2003) Design of a novel globular protein fold with atomic-level accuracy. Science 302:1364–1368PubMedCrossRef

10.

Mitelman F, Johansson B, Mertens F (eds) (2009) Mitelman database of chromosome aberrations in cancer. http://cgap.nci.nih.gov/Chromosomes/Mitelman

11.

Law ME, Templeton KL, Kitange G et al (2005) Molecular cytogenetic analysis of chromosomes 1 and 19 in glioma cell lines. Cancer Genet Cytogenet 160:1–14PubMedCrossRef

12.

Su AI, Cooke MP, Ching KA et al (2002) Large-scale analysis of the human and mouse transcriptomes. Proc Natl Acad Sci USA 99:4465–4470PubMedCrossRef

13.

Vogler M, Giagkousiklidis S, Genze F, Gschwend JE, Debatin KM, Fulda S (2005) Inhibition of clonogenic tumor growth: a novel function of Smac contributing to its antitumor activity. Oncogene 24:7190–7202PubMedCrossRef

14.

Planque N (2006) Nuclear trafficking of secreted factors and cell-surface receptors: new pathways to regulate cell proliferation and differentiation, and involvement in cancers. Cell Commun Signal 4:7PubMedCrossRef

15.

Brandenberger R, Wei H, Zhang S et al (2004) Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. Nat Biotechnol 22:707–716PubMedCrossRef

16.

Ward RM, Dirks PB (2007) Cancer stem cells: at the headwaters of tumor development. Annu Rev Pathol 2:175–189PubMedCrossRef

17.

Lal A, Lash AE, Altschul SF et al (1999) A public database for gene expression in human cancers. Cancer Res 59:5403–5407PubMed

18.

Boon K, Osório E, Greenhut SF et al (2002) An anatomy of normal and malignant gene expression. Proc Natl Acad Sci USA 99:11287–11292PubMedCrossRef

19.

Smith I S, Tachibana HK, Lee J et al (2000) Mapping of the chromosome 19 q-arm glioma tumor suppressor gene using fluorescence in situ hybridization and novel microsatellite markers. Genes Chromosom Cancer 29:16–25CrossRef

20.

von Deimling A, Nagel J, Bender B et al (1994) Deletion mapping of chromosome 19 in human gliomas. Int J Cancer 57(5):676–680CrossRef

21.

Kälin RE, Kretz MP, Meyer AM et al (2007) Paracrine and autocrine mechanisms of apelin signaling govern embryonic and tumor angiogenesis. Dev Biol 305:599–614PubMedCrossRef

22.

Cheng H, Liu P, Wang ZC et al (2009) SIK1 couples LKB1 to p53-dependent anoikis and suppresses metastasis. Sci Signal 2:ra35PubMedCrossRef

23.

Kuno K, Bannai K, Hakozaki M et al (2004) The carboxyl-terminal half region of ADAMTS-1 suppresses both tumorigenicity and experimental tumor metastatic potential. Biochem Biophys Res Commun 319:1327–1333PubMedCrossRef

24.

Lee YJ, Koch M, Karl D et al (2010) Variable inhibition of thrombospondin 1 against liver and lung metastases through differential activation of metalloproteinase ADAMTS1. Cancer Res 70:948–956PubMedCrossRef

25.

Smith JS, Aderete B, Minn Y et al (1999) Localization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype. Oncogene 18:4144–4152PubMedCrossRef

26.

Yang P, Kollmeyer TM, Buckner K, Bamlet W, Ballman KV, Jenkins RB (2005) Polymorphisms in GLTSCR1 and ERCC2 are associated with the development of oligodendrogliomas. Cancer 103:2363–2372PubMedCrossRef

27.

Wolf RM, Draghi N, Liang X et al (2003) p190RhoGAP can act to inhibit PDGF-induced gliomas in mice: a putative tumor suppressor encoded on human chromosome 19q13.3. Genes Dev 17:476–487PubMedCrossRef

Title: hHSS1: a novel secreted factor and suppressor of glioma growth located at chromosome 19q13.33
Authors: Katiana S. Junes-Gill
Timothy K. Gallaher
Zoya Gluzman-Poltorak
Joseph D. Miller
Christopher J. Wheeler
Xuemo Fan
Lena A. Basile
Publication date: 01-04-2011
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 2/2011
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-010-0314-6

At a glance: The STEP trials

Springer Medicine

hHSS1: a novel secreted factor and suppressor of glioma growth located at chromosome 19q13.33

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2011

Determination of the methylation status of MGMT in different regions within glioblastoma multiforme

Factors associated with preservation of facial nerve function after surgical resection of vestibular schwannoma

Erratum to: Radiation-induced changes in peripheral nerve by stereotactic radiosurgery: a study on the sciatic nerve of rabbit

Radiation-induced changes in peripheral nerve by stereotactic radiosurgery: a study on the sciatic nerve of rabbit

Correlation between O6-methylguanine-DNA methyltransferase and survival in elderly patients with glioblastoma treated with radiotherapy plus concomitant and adjuvant temozolomide

Effects of estrogen receptor antagonist on biological behavior and expression of growth factors in the prolactinoma MMQ cell line