Heparan sulfate in angiogenesis: a target for therapy

Wijk, Xander M R van; Kuppevelt, Toin H. Van

doi:10.1007/s10456-013-9401-6

Cited by 44 publications

(49 citation statements)

References 265 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since 3-OS HS facilitates HCMV infection, its further potential in overall disease development, especially in immune modulation or angiogenesis, can be further investigated using corneal endothelial cells (42). Several lines of evidence already suggest that sulfated HS plays a critical role during multiple pathophysiological processes, including inflammation and vascular angiogenesis (43)(44)(45). Our study provides a unique example of a naturally susceptible cell type that HCMV targets.…”

Section: Expression Of 3-ost Enzymes In His Cells Enhances Fusion Witmentioning

confidence: 87%

A Role for 3- O -Sulfated Heparan Sulfate in Promoting Human Cytomegalovirus Infection in Human Iris Cells

Baldwin

Maus

Zanotti

et al. 2015

J Virol

View full text Add to dashboard Cite

H uman cytomegalovirus (HCMV), a member of the betaherpesvirus family, is the leading cause of congenital neurological complications in neonates as a result of maternal infection (1-4). Among immunocompromised patients-especially those with an organ transplant, chemotherapy, or AIDS-the reactivation of virus causes life-threatening diseases, such as gastroenteritis, encephalitis, pneumonitis, and graft rejection (5-7). In addition, HCMV infection is also implicated in widespread ocular damage and potential vision loss from retinitis, anterior uveitis, and corneal endotheliitis (8-11). Because HCMV infection of the iris is a risk factor during anterior uveitis, understanding the dynamics of viral infection at the molecular level becomes relevant for understanding the viral pathogenesis in general and developing novel strategies to prevent blindness. Therefore, we used primary cultures of human iris stromal (HIS) cells as a model to determine the susceptibility and role of 3-O-sulfated heparan sulfate (3-OS HS) during HCMV uveitis.Although HCMV entry into host cells is poorly understood (12, 13), it is clearly a multistep process that requires complex interactions between viral envelope glycoproteins and the host cell receptors (12). It has been suggested that HCMV glycoprotein B (gB) binds to heparan sulfate (HS) during viral attachment, resulting in a high virion concentration at the cell surface and further binding to the cellular receptor (14-17). This interaction has been proposed to modulate immune responses (14, 18). To date, three receptors, epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor ␣ (PDGFR␣), and cellular integrins (␣2␤1, ␣6␤1, and ␣v␤3), have been implicated during HCMV entry (19)(20)(21)(22)(23)(24). In addition, recent studies have suggested the potential role of a sulfated form of HS during HCMV entry. For instance, a library of peptides derived from human hemofiltrate and screened for inhibitory effects on HCMV infection implicated the role of 6-O-sulfated HS (6-OS HS) (25) in HCMV entry. Similarly, a peptide generated against 3-OS HS using phage display library screening blocked HCMV entry (26). In addition, several sulfated polysaccharides (dextran sulfate, pentosan polysulfate, and heparin), copolymers of acrylic acid with vinyl alcohol sulfate, and 3-O-sulfated saccharide have proved to be potent inhibitors of HCMV infectivity in vitro (17,27). In this study, we investigated the susceptibility of HIS cells to HCMV infection and the role of 3-OS HS during this process. Our data demonstrate the significance of 3-OS HS during HCMV entry, and we propose a unique in vitro model for future studies related to 3-OS HS-dependent induction of proinflammatory cytokines and virus tropism.Susceptibility of primary cultures of HIS cells to HCMV infection. The HIS cultures were prepared in accordance with institutional review board-approved protocols and were isolated from anonymously donated human eyes (provided by the Illinois Eye Bank, Chicago, IL) via sterile dissecti...

show abstract

Section: Expression Of 3-ost Enzymes In His Cells Enhances Fusion Witmentioning

confidence: 87%

A Role for 3- O -Sulfated Heparan Sulfate in Promoting Human Cytomegalovirus Infection in Human Iris Cells

Baldwin

Maus

Zanotti

et al. 2015

J Virol

View full text Add to dashboard Cite

show abstract

“…Thus, it is evident why this enzyme may be an effective and attractive drug target. 32 , 35 Several HPSE inhibitors have been developed, and some of them have undergone clinical trials showing efficacy against tumors. 32 …”

Section: Discussionmentioning

confidence: 99%

“…Preclinical and clinical studies have demonstrated that therapies targeting the HPSE/SDC1 axis hold promise for blocking the aggressive behavior of cancer. 16 , 35 SDC1 plays a crucial role in carcinogenesis and is an attractive target for anticancer treatment with HPSE inhibitors and immunotherapy with anti-SDC1 antibodies. 17 , 36 …”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical expression of heparanase isoforms and syndecan-1 proteins in colorectal adenomas

Waisberg¹,

Theodoro²,

Matos³

et al. 2016

Eur J Histochem

View full text Add to dashboard Cite

The proteoglycan syndecan-1 and the endoglucuronidases heparanase-1 and heparanase-2 are involved in molecular pathways that deregulate cell adhesion during carcinogenesis. Few studies have examined the expression of syndecan-1, heparanase-1 and mainly heparanase-2 proteins in non-neoplastic and neoplastic human colorectal adenoma tissues. The aim of this study was to analyze the correlation among the heparanase isoforms and the syndecan-1 proteins through immunohistochemical expression in the tissue of colorectal adenomas. Primary antihuman polyclonal anti-HPSE and anti-HPSE2 antibodies and primary anti-human monoclonal anti-SDC1 antibody were used in the immunohistochemical study. The expressions of heparanase-1 and heparanase-2 proteins were determined in tissue samples from 65 colorectal adenomas; the expression of syndecan-1 protein was obtained from 39 (60%) patients. The histological type of adenoma was tubular in 44 (67.7%) patients and tubular-villous in 21 (32.3%); there were no villous adenomas. The polyps were <1.0 cm in size in 54 (83.1%) patients and ≥1.0 cm in 11 (16.9%). The images were quantified by digital counter with a computer program for this purpose. The expression index represented the relationship between the intensity expression and the percentage of positively stained cells. The results showed that the average of heparanase-1, heparanase-2 and syndecan-1 expression index was 73.29 o.u./µm², 93.34 o.u./µm², and 55.29 o.u./µm², respectively. The correlation between the heparanase-1 and syndecan-1 expression index was positive (R=0.034) and significant (P=0.035). There was a negative (R= -0.384) and significant (P=0.016) correlation between the expression index of heparanase-1 and heparanase-2. A negative (R= -0.421) and significant (P=0.008) correlation between the expression index of heparanase-2 and syndecan-1 was found. We concluded that in colorectal adenomas, the heparanase-1 does not participate in syndecan-1 degradation; the heparanase-2 does not stimulate syndecan-1 degradation by the action of heparanase-1, and the heparanase-2 may be involved in the modulation of the heparanase-1 activity.

show abstract

“…For example, 6‐ O ‐sulfated CS disaccharides are increased up to 50‐fold in gastrointestinal carcinoma (4), and 6‐ O ‐sulfated and 4‐ O ‐, 6‐ O ‐disulfated CS structures are elevated in ovarian cancer (5, 6). Furthermore, HS 6‐ O sulfation is of significant importance in fibroblast growth factor (FGF)‐2/vascular endothelial growth factor (VEGF) signaling (7) and (tumor) angiogenesis (8), and silencing of HS 6‐ O ‐sulfotransferase‐2 inhibits angiogenesis and tumorigenesis in mice (9, 10). These effects underscore the need for compounds that can interfere with GAG function, biosynthesis, and specific sulfation.…”

Section: Introductionmentioning

confidence: 99%

A common sugar‐nucleotide‐mediated mechanism of inhibition of (glycosamino)glycan biosynthesis, as evidenced by 6F‐GalNAc (Ac ₃ )

et al. 2015

View full text Add to dashboard Cite

Glycosaminoglycan (GAG) polysaccharides have been implicated in a variety of cellular processes, and alterations in their amount and structure have been associated with diseases such as cancer. In this study, we probed 11 sugar analogs for their capacity to interfere with GAG biosynthesis. One analog, with a modification not directly involved in the glycosidic bond formation, 6F-N-acetyl-d-galactosamine (GalNAc) (Ac3), was selected for further study on its metabolic and biologic effect. Treatment of human ovarian carcinoma cells with 50 μM 6F-GalNAc (Ac3) inhibited biosynthesis of GAGs (chondroitin/dermatan sulfate by ∼50-60%, heparan sulfate by ∼35%), N-acetyl-d-glucosamine (GlcNAc)/GalNAc containing glycans recognized by the lectins Datura stramonium and peanut agglutinin (by ∼74 and ∼43%, respectively), and O-GlcNAc protein modification. With respect to function, 6F-GalNAc (Ac3) treatment inhibited growth factor signaling and reduced in vivo angiogenesis by ∼33%. Although the analog was readily transformed in cells into the uridine 5'-diphosphate (UDP)-activated form, it was not incorporated into GAGs. Rather, it strongly reduced cellular UDP-GalNAc and UDP-GlcNAc pools. Together with data from the literature, these findings indicate that nucleotide sugar depletion without incorporation is a common mechanism of sugar analogs for inhibiting GAG/glycan biosynthesis.

show abstract

Heparan sulfate in angiogenesis: a target for therapy

Cited by 44 publications

References 265 publications

A Role for 3- O -Sulfated Heparan Sulfate in Promoting Human Cytomegalovirus Infection in Human Iris Cells

A Role for 3- O -Sulfated Heparan Sulfate in Promoting Human Cytomegalovirus Infection in Human Iris Cells

Immunohistochemical expression of heparanase isoforms and syndecan-1 proteins in colorectal adenomas

A common sugar‐nucleotide‐mediated mechanism of inhibition of (glycosamino)glycan biosynthesis, as evidenced by 6F‐GalNAc (Ac ₃ )

Contact Info

Product

Resources

About

Heparan sulfate in angiogenesis: a target for therapy

Cited by 44 publications

References 265 publications

A Role for 3- O -Sulfated Heparan Sulfate in Promoting Human Cytomegalovirus Infection in Human Iris Cells

A Role for 3- O -Sulfated Heparan Sulfate in Promoting Human Cytomegalovirus Infection in Human Iris Cells

Immunohistochemical expression of heparanase isoforms and syndecan-1 proteins in colorectal adenomas

A common sugar‐nucleotide‐mediated mechanism of inhibition of (glycosamino)glycan biosynthesis, as evidenced by 6F‐GalNAc (Ac 3 )

Contact Info

Product

Resources

About

A common sugar‐nucleotide‐mediated mechanism of inhibition of (glycosamino)glycan biosynthesis, as evidenced by 6F‐GalNAc (Ac ₃ )