Osteopontin stimulates a subpopulation of quiescent human prostate epithelial cells with high proliferative potential to divide in vitro

Elgavish, Ada; Prince, Charles W.; Chang, Ping‐Ying; Lloyd, Keith; Lindsey, Russell; Reed, Rebecca

doi:10.1002/(sici)1097-0045(19980501)35:2<83::aid-pros1>3.0.co;2-h

Cited by 39 publications

(11 citation statements)

References 49 publications

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“…Others have previously shown that osteopontin stimulates melanoma and prostate tumor cell proliferation [19,20]. Our data show that OPN overexpressing colon cancer cells are more proliferative in vitro and derived tumors grow faster in vivo.…”

Section: Proliferation and Tumor Growth Rates Of Cells Expressing Higsupporting

confidence: 63%

Osteopontin regulates multiple functions contributing to human colon cancer development and progression

Irby

McCarthy

Yeatman

2004

Clin Exp Metastasis

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Osteopontin (OPN) is a secreted phosphoglycoprotein known to interact with a number of integrin receptors. While increased OPN expression has been reported in a number of human cancers, and its cognate receptors (alphav-beta3, alphav-beta5, and alphav-beta1 integrins and CD44) have been identified, its role in colon cancer development and progression has not been extensively studied. We previously identified, using a combination of gene expression and tissue microarrays, that increased OPN expression is concordant with tumor stage. The current study examined the functional role of OPN in colon cancer progression and metastatic potential. The principal findings of this study were that both endogenous OPN expression (via stable transfection) as well as exogenous OPN (added to culture medium) enhanced the motility and invasive capacity of human colon cancer cells in vitro. OPN appeared to regulate motility though interaction with CD44. OPN expression also reduced intercellular (homotypic) adhesion, an important characteristic of metastatic cancer cells. Stable transfection of four poorly tumorigenic human colon cancer cell lines with OPN also resulted in enhanced tumorigenicity in vivo with increased proliferation and increased CD31 positive microvessel counts, concordant with the degree of OPN expression. Collectively, these results suggest that OPN may affect multiple functional components contributing to human colon cancer progression and solidifies its role in this process.

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Section: Proliferation and Tumor Growth Rates Of Cells Expressing Higsupporting

confidence: 63%

Osteopontin regulates multiple functions contributing to human colon cancer development and progression

Irby

McCarthy

Yeatman

2004

Clin Exp Metastasis

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“…These interactions may explain how intracellular OPN mediates cell migration. However, there is also evidence that suggests that intracellular OPN has other cellular functions, particularly in relation to cell proliferation (8,25,26,28).…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, glucose-and hypoxia-induced DNA synthesis in mesangial cells is inhibited by OPN neutralization (20). More direct evidence for OPN's mitogenic capacity was provided by its ability to stimulate division of previously quiescent prostatic cells (8). Enhanced expression of OPN is not limited to isolated cells in culture, inasmuch as OPN localizes to actively proliferating cells in animal models of renal, vascular, and periodontal tissue injury and regeneration (16,17,27,29).…”

mentioning

confidence: 99%

Osteopontin localizes to the nucleus of 293 cells and associates with polo-like kinase-1

Junaid¹,

Moon²,

Harding³

et al. 2007

American Journal of Physiology-Cell Physiology

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Osteopontin (OPN) is a secreted phosphoprotein involved in cellular proliferation and associated with tumor progression. Although an intracellular form of OPN has been described, its function remains unknown. In this study, a novel nuclear location for intracellular OPN and a correlation with cell division were demonstrated. OPN distinctly localized to the nucleus in a subset of transiently transfected human embryonic kidney 293 cells. Immunoblotting confirmed the nuclear location of native OPN, and results from immunofluorescence studies suggested an association between nuclear OPN and cell cycle progression. Flow cytometry revealed that nuclear and cellular OPN content rose significantly during the S and G(2)/M phases, respectively. Treatment of cells with the DNA polymerase inhibitor aphidicolin prevented cell cycling and greatly reduced cellular OPN content. The intracellular location of OPN coincided with polo-like kinase-1 (Plk-1), a member of the polo-like kinase family, which, in part through their regulation of centrosome-related events, are integral to successful cellular mitosis. OPN and Plk-1 were coimmunoprecipitated from nuclear, but not cystoslic, extracts, demonstrating an interaction that is limited to the nucleus, presumably during mitosis. Deletion of the COOH terminus of OPN militated against nuclear localization and Plk-1 interaction. Elevated expression of OPN was also associated with an increase in the number of multinucleate 293 cells, whereas transfection of the COOH-terminal-deleted OPN decreased the percentage of multinucleate cells below basal levels. These findings implicate intranuclear OPN as a participant in the process of cell duplication.

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“…Ligation of integrins such as (x 33 1996), which is t by OPN leads to phosphorylation of focal adhesion hyaluronate. CD44 ar kinase (FAK) (Frisch et al, 1996: Craig andJohnson, 1996), sively studied as a ca paxillin, tensin, and Src (Lopez et al, 1995), which initicluding myeloid ce ates signals for proliferation, cytoskeletal organization, (Elgavish et al, 1998). Ras, P13-kinase, and Akt pathways activated by V03-mediated cell attachment have also been implicated in cell survival (Khwaja and Downward, 1997), as have MEKK-I/INK (Cardone ct al., 1997) and Bcl-2 (Stromblad et al, 1996). That OPN can prevent cell death was first indicated in studies of kidney proximal tubule epithelial cells exposed to hypoxia and re-oxygenation .…”

Section: Through Integrinsmentioning

confidence: 99%

Osteopontin

Sodek

Ganss²,

McKee

2000

Critical Reviews in Oral Biology & Medicine

1,030

960

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Osteopontin (OPN) is a highly phosphorylated sialoprotein that is a prominent component of the mineralized extracellular matrices of bones and teeth. OPN is characterized by the presence of a polyaspartic acid sequence and sites of Ser/Thr phosphorylation that mediate hydroxyapatite binding, and a highly conserved RGD motif that mediates cell attachment/signaling. Expression of OPN in a variety of tissues indicates a multiplicity of functions that involve one or more of these conserved motifs. While the lack of a clear phenotype in OPN "knockout" mice has not established a definitive role for OPN in any tissue, recent studies have provided some novel and intriguing insights into the versatility of this enigmatic protein in diverse biological events, including developmental processes, wound healing, immunological responses, tumorigenesis, bone resorption, and calcification. The ability of OPN to stimulate cell activity through multiple receptors linked to several interactive signaling pathways can account for much of the functional diversity. In this review, we discuss the structural features of OPN that relate to its function in the formation, remodeling, and maintenance of bones and teeth.

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Osteopontin stimulates a subpopulation of quiescent human prostate epithelial cells with high proliferative potential to divide in vitro

Cited by 39 publications

References 49 publications

Osteopontin regulates multiple functions contributing to human colon cancer development and progression

Osteopontin regulates multiple functions contributing to human colon cancer development and progression

Osteopontin localizes to the nucleus of 293 cells and associates with polo-like kinase-1

Osteopontin

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