title: Expression of the SIBLINGs and their MMP partners in human benign and malignant prostate neoplasms.
abstract: The small integrin binding ligands n-linked glycoproteins (SIBLINGs) have emerged as potential diagnostic and prognostic indices, and as key targets, in cancer therapy. Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. The other two family members are dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE). The specific SIBLING-MMP pairing reported in some cancers have not been reported in prostate neoplasms. In this study, we investigated SIBLING-MMP expression and potential interaction in prostate neoplasms. Chi square analysis of immunohistochemistry results showed significant upregulation of OPN (X2=25.710/p<0.001), BSP (X2=19.546/p<0.001), and DSPP (X2=8.720/p=0.003) in prostate adenocarcinoma (pAdC). MEPE was significantly upregulated in benign prostate hyperplasia (BPH; X2=44.153/p<0.001). There were no significant differences in MMP expression between BPH and pAdC. Western blot analysis showed significantly elevated BSP and DSPP in prostate cancer-derived cells. Immunofluorescence studies confirmed BSP-MMP2, OPN-MMP3, and DMP1-MMP9 coexpression in two cancer-derived cell lines, whereas in situ proximity ligation assays confirmed potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC. Our reports provide evidence that SIBLING-MMP interaction may play a role in the progression of BPH to pAdC.
authors.affiliation: Department of Anatomic and Molecular Pathology, College of Medicine, University of Lagos, Lagos, Nigeria.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Anunobi
authors.affiliation: Department of Diagnostic and Biomedical Sciences, The University of Texas Health Science Center at Houston, School of Dentistry, Houston, Texas, U.S.A.
authors.forename: Komal
authors.initials: K
authors.lastname: Koli
authors.affiliation: Department of Diagnostic and Biomedical Sciences, The University of Texas Health Science Center at Houston, School of Dentistry, Houston, Texas, U.S.A.
authors.forename: Geetu
authors.initials: G
authors.lastname: Saxena
authors.affiliation: Department of Anatomic and Molecular Pathology, College of Medicine, University of Lagos, Lagos, Nigeria.
authors.forename: Adekunbiola A
authors.initials: AA
authors.lastname: Banjo
authors.affiliation: Department of Diagnostic and Biomedical Sciences, The University of Texas Health Science Center at Houston, School of Dentistry, Houston, Texas, U.S.A.
authors.forename: Kalu U E
authors.initials: KU
authors.lastname: Ogbureke
mesh_terms: D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000378:metabolism; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000378:metabolism; D000099311:Dentin Sialophosphoprotein
chemical_list: D016326:Extracellular Matrix Proteins; D020782:Matrix Metalloproteinases; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein
keywords: SIBLING-MMP interaction; SIBLINGs; dentin sialophosphoprotein; matrix metalloproteinases; prostate cancer