Limits...
Heparanase regulates levels of syndecan-1 in the nucleus.

Chen L, Sanderson RD - PLoS ONE (2009)

Bottom Line: This effect requires enzymatically active heparanase because cells expressing high levels of mutated, enzymatically inactive heparanase, failed to diminish syndecan-1 levels in the nucleus.Although heparan sulfate function within the nucleus is not well understood, there is emerging evidence that it may act to repress transcriptional activity.The resulting changes in gene expression facilitated by the loss of nuclear syndecan-1 could explain how heparanase enhances expression of MMP-9, VEGF, tissue factor and perhaps other effectors that condition the tumor microenvironment to promote an aggressive cancer phenotype.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.

ABSTRACT
Syndecan-1 is a transmembrane heparan sulfate-bearing proteoglycan known to regulate multiple biological functions at the cell surface and within the extracellular matrix. Its functional activity can be modulated by heparanase, an enzyme that cleaves heparan sulfate chains and whose expression has been associated with an aggressive phenotype in many cancers. In addition to remodeling syndecan-1 by cleaving its heparan sulfate chains, heparanase influences syndecan-1 location by upregulating expression of enzymes that accelerate its shedding from the cell surface. In the present study we discovered that heparanase also alters the level of nuclear syndecan-1. Upon upregulation of heparanase expression or following addition of recombinant heparanase to myeloma cells, the nuclear localization of syndecan-1 drops dramatically as revealed by confocal microscopy, western blotting and quantification by ELISA. This effect requires enzymatically active heparanase because cells expressing high levels of mutated, enzymatically inactive heparanase, failed to diminish syndecan-1 levels in the nucleus. Although heparan sulfate function within the nucleus is not well understood, there is emerging evidence that it may act to repress transcriptional activity. The resulting changes in gene expression facilitated by the loss of nuclear syndecan-1 could explain how heparanase enhances expression of MMP-9, VEGF, tissue factor and perhaps other effectors that condition the tumor microenvironment to promote an aggressive cancer phenotype.

Show MeSH

Related in: MedlinePlus

Syndecan-1 is not detected within the nucleus of cells expressing high levels of heparanase.Confocal microscopic z-stack images of (A) HPSE-low and (B) HPSE-high cells immunostained using antibody to syndecan-1. Blue (Hoechst stain) identifies nuclei; white identifies syndecan-1 within the nucleus (co-localization of Hoechst and syndecan-1); green identifies cytoplasmic and cell surface syndecan-1. Syndecan-1 is detected within nuclei of HPSE-low cells but absent in nuclei of the HPSE-high cells. Bar = 10 µm. Note: As is characteristic of myeloma cells, the size of the nucleus is large relative to the amount of cytoplasm.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2654539&req=5

pone-0004947-g001: Syndecan-1 is not detected within the nucleus of cells expressing high levels of heparanase.Confocal microscopic z-stack images of (A) HPSE-low and (B) HPSE-high cells immunostained using antibody to syndecan-1. Blue (Hoechst stain) identifies nuclei; white identifies syndecan-1 within the nucleus (co-localization of Hoechst and syndecan-1); green identifies cytoplasmic and cell surface syndecan-1. Syndecan-1 is detected within nuclei of HPSE-low cells but absent in nuclei of the HPSE-high cells. Bar = 10 µm. Note: As is characteristic of myeloma cells, the size of the nucleus is large relative to the amount of cytoplasm.

Mentions: Using confocal microscopy we noted that syndecan-1 was localized within the nucleus of CAG myeloma cells expressing low levels of heparanase (HPSE-low cells) but it not present within the nucleus of CAG cells expressing high levels of heparanase (HPSE-high cells) (Fig. 1). Cytoplasmic staining for syndecan-1 was present in both HPSE-low and HPSE-high cells but was more prominent in the HPSE-low cells. Both HPSE-low and HPSE-high cells exhibited bright staining on the cell surface, often in patches (Fig. 1). This cell surface pattern of staining is consistent with our previous finding that syndecan-1 is often found concentrated on uropods, structures present at the trailing edge of motile cells [19].


Heparanase regulates levels of syndecan-1 in the nucleus.

Chen L, Sanderson RD - PLoS ONE (2009)

Syndecan-1 is not detected within the nucleus of cells expressing high levels of heparanase.Confocal microscopic z-stack images of (A) HPSE-low and (B) HPSE-high cells immunostained using antibody to syndecan-1. Blue (Hoechst stain) identifies nuclei; white identifies syndecan-1 within the nucleus (co-localization of Hoechst and syndecan-1); green identifies cytoplasmic and cell surface syndecan-1. Syndecan-1 is detected within nuclei of HPSE-low cells but absent in nuclei of the HPSE-high cells. Bar = 10 µm. Note: As is characteristic of myeloma cells, the size of the nucleus is large relative to the amount of cytoplasm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2654539&req=5

pone-0004947-g001: Syndecan-1 is not detected within the nucleus of cells expressing high levels of heparanase.Confocal microscopic z-stack images of (A) HPSE-low and (B) HPSE-high cells immunostained using antibody to syndecan-1. Blue (Hoechst stain) identifies nuclei; white identifies syndecan-1 within the nucleus (co-localization of Hoechst and syndecan-1); green identifies cytoplasmic and cell surface syndecan-1. Syndecan-1 is detected within nuclei of HPSE-low cells but absent in nuclei of the HPSE-high cells. Bar = 10 µm. Note: As is characteristic of myeloma cells, the size of the nucleus is large relative to the amount of cytoplasm.
Mentions: Using confocal microscopy we noted that syndecan-1 was localized within the nucleus of CAG myeloma cells expressing low levels of heparanase (HPSE-low cells) but it not present within the nucleus of CAG cells expressing high levels of heparanase (HPSE-high cells) (Fig. 1). Cytoplasmic staining for syndecan-1 was present in both HPSE-low and HPSE-high cells but was more prominent in the HPSE-low cells. Both HPSE-low and HPSE-high cells exhibited bright staining on the cell surface, often in patches (Fig. 1). This cell surface pattern of staining is consistent with our previous finding that syndecan-1 is often found concentrated on uropods, structures present at the trailing edge of motile cells [19].

Bottom Line: This effect requires enzymatically active heparanase because cells expressing high levels of mutated, enzymatically inactive heparanase, failed to diminish syndecan-1 levels in the nucleus.Although heparan sulfate function within the nucleus is not well understood, there is emerging evidence that it may act to repress transcriptional activity.The resulting changes in gene expression facilitated by the loss of nuclear syndecan-1 could explain how heparanase enhances expression of MMP-9, VEGF, tissue factor and perhaps other effectors that condition the tumor microenvironment to promote an aggressive cancer phenotype.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.

ABSTRACT
Syndecan-1 is a transmembrane heparan sulfate-bearing proteoglycan known to regulate multiple biological functions at the cell surface and within the extracellular matrix. Its functional activity can be modulated by heparanase, an enzyme that cleaves heparan sulfate chains and whose expression has been associated with an aggressive phenotype in many cancers. In addition to remodeling syndecan-1 by cleaving its heparan sulfate chains, heparanase influences syndecan-1 location by upregulating expression of enzymes that accelerate its shedding from the cell surface. In the present study we discovered that heparanase also alters the level of nuclear syndecan-1. Upon upregulation of heparanase expression or following addition of recombinant heparanase to myeloma cells, the nuclear localization of syndecan-1 drops dramatically as revealed by confocal microscopy, western blotting and quantification by ELISA. This effect requires enzymatically active heparanase because cells expressing high levels of mutated, enzymatically inactive heparanase, failed to diminish syndecan-1 levels in the nucleus. Although heparan sulfate function within the nucleus is not well understood, there is emerging evidence that it may act to repress transcriptional activity. The resulting changes in gene expression facilitated by the loss of nuclear syndecan-1 could explain how heparanase enhances expression of MMP-9, VEGF, tissue factor and perhaps other effectors that condition the tumor microenvironment to promote an aggressive cancer phenotype.

Show MeSH
Related in: MedlinePlus