Osteopontin‐c is a selective marker of breast cancer

Mirza, M. B.; Shaughnessy, Elizabeth; Hurley, John K.; Vanpatten, Kristie A.; Pestano, Gary A.; He, Bin; Weber, Georg F.

doi:10.1002/ijc.23204

Cited by 123 publications

(144 citation statements)

References 23 publications

(30 reference statements)

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“…Similarly, OPN-c was expressed at high levels in a small number of colon carcinoma samples and at moderate levels in tumour-adjacent tissue, while OPN-a was expressed at very low levels in tumour tissue (Mirza et al 2008). These studies emphasize the variability amongst OPN isoform expression in different types of cancer.…”

Section: Expression Of Opn Isoforms In Human Tumoursmentioning

confidence: 67%

Pre- and post-translational regulation of osteopontin in cancer

Anborgh¹,

Mutrie

Tuck

et al. 2011

J. Cell Commun. Signal.

104

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Osteopontin (OPN) is a matricellular protein that binds to a number of cell surface receptors including integrins and CD44. It is expressed in many tissues and secreted into body fluids including blood, milk and urine. OPN plays important physiological roles in bone remodeling, immune response and inflammation. It is also a tumour-associated protein, and elevated OPN levels are associated with tumour formation, progression and metastasis. Research has revealed a promising role for OPN as a cancer biomarker. OPN is subject to alternative splicing, as well as post-translational modifications such as phosphorylation, glycosylation and proteolytic cleavage. Functional differences have been revealed for different isoforms and post-translational modifications. The pattern of isoform expression and post-translational modification is cell-type specific and may influence the potential role of OPN in malignancy and as a cancer biomarker.

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Section: Expression Of Opn Isoforms In Human Tumoursmentioning

confidence: 67%

Pre- and post-translational regulation of osteopontin in cancer

Anborgh¹,

Mutrie

Tuck

et al. 2011

J. Cell Commun. Signal.

104

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“…OPN-c, which lacks exon 4, has been reported to be expressed selectively in tumor tissues and correlated with tumor grade (52)(53)(54)(55)(56). Whereas OPN-a aggregates and enhances cell adhesion and therefore attenuates dissemination of tumor cells, OPN-c supports tumor invasion because of its lack of aggregation (52).…”

Section: Discussionmentioning

confidence: 99%

Osteopontin Undergoes Polymerization in Vivo and Gains Chemotactic Activity for Neutrophils Mediated by Integrin α9β1

Nishimichi

Hayashita-Kinoh

Chen

et al. 2011

Journal of Biological Chemistry

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Osteopontin (OPN) is an integrin-binding inflammatory cytokine that undergoes polymerization catalyzed by transglutaminase 2. We have previously reported that polymeric OPN (polyOPN), but not unpolymerized OPN (OPN*), attracts neutrophils in vitro by presenting an acquired binding site for integrin ␣9␤1. Among many in vitro substrates for transglutaminase 2, only a few have evidence for in vivo polymerization and concomitant function. Although polyOPN has been identified in bone and aorta, the in vivo functional significance of polyOPN is unknown. To determine whether OPN polymerization contributes to neutrophil recruitment in vivo, we injected OPN* into the peritoneal space of mice. Polymeric OPN was detected by immunoblotting in the peritoneal wash of mice injected with OPN*, and both intraperitoneal and plasma OPN* levels were higher in mice injected with a polymerization-incompetent mutant, confirming that OPN* polymerizes in vivo. OPN* injection induced neutrophil accumulation, which was significantly less following injection of a mutant OPN that was incapable of polymerization. The importance of in vivo polymerization was further confirmed with cystamine, a transglutaminase inhibitor, which blocked the polymerization and attenuated OPN*-mediated neutrophil recruitment. The thrombin-cleaved N-terminal fragment of OPN, another ligand for ␣9␤1, was not responsible for neutrophil accumulation because a thrombin cleavage-incompetent mutant recruited similar numbers of neutrophils as wild type OPN*. Neutrophil accumulation in response to both wild type and thrombin cleavage-incompetent OPN* was reduced in mice lacking the integrin ␣9 subunit in leukocytes, indicating that ␣9␤1 is required for polymerization-induced recruitment. We have illustrated a physiological role of molecular polymerization by demonstrating acquired chemotactic properties for OPN. Osteopontin (OPN),3 an integrin-binding cytokine, plays critical roles in physiological and pathological processes, including inflammation, immunomodulation, tissue remodeling, fibrosis, mineralization (1), stem cell retention (2), and tumor metastasis (3). These functions are exerted through interactions with nine integrins and CD44 (4). OPN undergoes many types of post-translational modification, including phosphorylation (5), glycosylation, transglutamination (6), and proteolytic cleavage. Among these post-translational modifications, transglutamination (7) and thrombin-cleavage (8, 9) enhance interactions with integrins. Thrombin-cleaved N-terminal fragment of OPN (nOPN) has been found to play roles in rheumatoid arthritis (10, 11), autoimmune hepatitis (12), and stem cell retention in the bone marrow niche (2). Although OPN was found as a substrate for transglutaminase 2 (TG2; EC 2.3.2.13) earlier than thrombin, little is known about the functional role of the product of transglutamination, polymeric OPN. TG2 is a cross-linking enzyme that catalyzes isopeptide bonding between Gln and Lys residues (13) with specificity for amino acid sequences containing Gln (...

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“…By contrast, the full-length form osteopontin-a is present in both breast cancers and nontransformed breast tissue. 28,49 One role for osteopontin in tumor progression is the support of anchorage-independence. Osteopontin-c is never expressed without the full-length form osteopontin-a, and the two variants may synergize in supporting the survival of circulating tumor cells.…”

Section: A Metabolic Role For the Metastasis Gene Osteopontinmentioning

confidence: 99%

Metabolism in cancer metastasis

Weber

2015

Int. J. Cancer

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Cancer metabolism has regained substantial research interest over recent years. The focus has been mostly on the primary tumor, while metabolic adjustments during dissemination have been less extensively researched. Deadhesion impairs glucose transport and brings about an ATP deficit that leads to apoptosis. To survive, metastasizing cancer cells need to increase ATP synthesis, which involves mitochondrial activity and is accomplished in part through peroxide signaling. This change in metabolism, associated with cancer spread, is different from the Warburg effect. Therefore it is important to distinguish between the metabolic adjustments in primary tumor cells and those in disseminating tumor cells. In general, it is likely that metabolic responses to environmental cues commonly occur in cell biology.

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Osteopontin‐c is a selective marker of breast cancer

Cited by 123 publications

References 23 publications

Pre- and post-translational regulation of osteopontin in cancer

Pre- and post-translational regulation of osteopontin in cancer

Osteopontin Undergoes Polymerization in Vivo and Gains Chemotactic Activity for Neutrophils Mediated by Integrin α9β1

Metabolism in cancer metastasis

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