Dentin Sialophosphoprotein (DSPP) Gene-Silencing Inhibits Key Tumorigenic Activities in Human Oral Cancer Cell Line, OSC2

Joshi, Rajeshree; Tawfik, Amany; Edeh, Nneka; McCloud, Veronica V.; Looney, Stephen W.; Lewis, Jill B.; Hsu, Stephen; Ogbureke, Kalu U.E.

doi:10.1371/journal.pone.0013974

Cited by 24 publications

(31 citation statements)

References 29 publications

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“…The expression of SIBLINGs is increased in cancer cells and therefore they are considered biomarkers for prostate cancer (17-20). The mechanisms involved in the increased expression of SIBLINGs in cancer cells are not fully understood, however, a recent in vitro study suggested that DSPP has the potential to activate oral carcinogenesis (21). …”

Section: The Features Of the Sibling Family And The Properties Of mentioning

confidence: 99%

Dentin sialophosphoprotein and dentin matrix protein-1: Two highly phosphorylated proteins in mineralized tissues

Suzuki

Haruyama

Nishimura

et al. 2012

Archives of Oral Biology

134

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Dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1) are highly phosphorylated proteins that belong to the family of small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and are essential for proper development of hard tissues such as teeth and bones. In order to understand how they contribute to tissue organization, DSPP and DMP-1 have been analyzed for over a decade using both in vivo and in vitro techniques. Among the five SIBLINGs, the DSPP and DMP-1 genes are located next to each other and their gene and protein structures are most similar. In this review we examine the phenotypes of the genetically engineered mouse models of DSPP and DMP-1 and also introduce complementary in vitro studies into the molecular mechanisms underlying these phenotypes. DSPP affects the mineralization of dentin more profoundly than DMP-1. In contrast, DMP-1 significantly affects bone mineralization and importantly controls serum phosphate levels by regulating serum FGF-23 levels, whereas DSPP does not show any systemic effects. DMP-1 activates integrin signaling and is endocytosed into the cytoplasm whereupon it is translocated to the nucleus. In contrast, DSPP only activates integrin-dependent signaling. Thus it is now clear that both DSPP and DMP-1 contribute to hard tissue mineralization and the tissues affected by each are different presumably as a result of their different expression levels. In fact, in comparison with DMP-1, the functional analysis of cell signaling by DSPP remains relatively unexplored.

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Section: The Features Of the Sibling Family And The Properties Of mentioning

confidence: 99%

Dentin sialophosphoprotein and dentin matrix protein-1: Two highly phosphorylated proteins in mineralized tissues

Suzuki

Haruyama

Nishimura

et al. 2012

Archives of Oral Biology

134

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“…A recent in vitro study suggested that the inhibition of endogenous DSPP expression repressed the carcinogenesis features of human oral squamous cells [46] , and the expression of DSPP was recently shown to be upregulated in several cancer tissues [4] , [47] , [48] . Aberrant conditions such as the release of intracellular proteases from cancer cells or a local low pH environment may degrade PP to generate the PP fragments included the RGD domain with an open amino- or carboxyl-terminal side.…”

Section: Discussionmentioning

confidence: 99%

Adhesive and Migratory Effects of Phosphophoryn Are Modulated by Flanking Peptides of the Integrin Binding Motif

et al. 2014

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Phosphophoryn (PP) is generated from the proteolytic cleavage of dentin sialophosphoprotein (DSPP). Gene duplications in the ancestor dentin matrix protein-1 (DMP-1) genomic sequence created the DSPP gene in toothed animals. PP and DMP-1 are phosphorylated extracellular matrix proteins that belong to the family of small integrin-binding ligand N-linked glycoproteins (SIBLINGs). Many SIBLING members have been shown to evoke various cell responses through the integrin-binding Arg-Gly-Asp (RGD) domain; however, the RGD-dependent function of PP is not yet fully understood. We demonstrated that recombinant PP did not exhibit any obvious cell adhesion ability, whereas the simultaneously purified recombinant DMP-1 did. A cell adhesion inhibitory analysis was performed by pre-incubating human osteosarcoma MG63 cells with various PP peptides before seeding onto vitronectin. The results obtained revealed that the incorporation of more than one amino acid on both sides of the PP-RGD domain was unable to inhibit the adhesion of MG63 cells onto vitronectin. Furthermore, the inhibitory activity of a peptide containing the PP-RGD domain with an open carboxyl-terminal side (H-463SDESDTNSESANESGSRGDA482-OH) was more potent than that of a peptide containing the RGD domain with an open amino-terminal side (H-478SRGDASYTSDESSDDDNDSDSH499-OH). This phenomenon was supported by the potent cell adhesion and migration abilities of the recombinant truncated PP, which terminated with Ala482. Furthermore, various point mutations in Ala482 and/or Ser483 converted recombinant PP into cell-adhesive proteins. Therefore, we concluded that the Ala482-Ser483 flanking sequence, which was detected in primates and mice, was the key peptide bond that allowed the PP-RGD domain to be sequestered. The differential abilities of PP and DMP-1 to act on integrin imply that DSPP was duplicated from DMP-1 to serve as a crucial extracellular protein for tooth development rather than as an integrin-mediated signaling molecule.

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“…Human Cell Lines and Culture Conditions SCC25 and OSC2 (OSCC), and DOK (dysplastic oral keratinocytes), and A818-6 (Human Pancreatic Adenocarcinoma) human cell lines have been published [15][16][17][18] and were initially obtained from American Type Culture Collection. The human oral keratinocyte (HOK) whole lysate was purchased from ScienCell TM Research Laboratories (cat.…”

Section: Discussionmentioning

confidence: 99%

Expression of p8 in Human Oral Squamous Cell Carcinoma

Bingham

Dickinson

Cray³

et al. 2014

Head and Neck Pathol

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The present study investigated the expression of p8, a transcription factor upregulated in some human cancers, in oral squamous cell carcinomas (OSCCs). Immunohistochemical analysis of p8 expression was carried out on 20 archived surgical specimens of human OSCCs, and expression correlated with clinical outcome parameters in a retrospective study. Expression of p8 in a number of OSCC cell lines also was investigated by western blot and RT-PCR analyses. p8 was expressed in 80 % (16/20) of the samples with levels of expression exhibiting a significant difference (v 2 = 8.352, df = 3, p = 0.039) by patient age. Furthermore, greater levels of p8 immunoreactivity was significantly associated with advanced tumor grade (p = 0.008). p8 also was upregulated in OSCC cell lines. p8 is expressed in a significant proportion of OSCCs, and in human OSCC cell lines, suggesting a potential value of p8 as a diagnostic and/prognostic tool for oral cancers.

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Dentin Sialophosphoprotein (DSPP) Gene-Silencing Inhibits Key Tumorigenic Activities in Human Oral Cancer Cell Line, OSC2

Cited by 24 publications

References 29 publications

Dentin sialophosphoprotein and dentin matrix protein-1: Two highly phosphorylated proteins in mineralized tissues

Dentin sialophosphoprotein and dentin matrix protein-1: Two highly phosphorylated proteins in mineralized tissues

Adhesive and Migratory Effects of Phosphophoryn Are Modulated by Flanking Peptides of the Integrin Binding Motif

Expression of p8 in Human Oral Squamous Cell Carcinoma

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