An iminosugar-based heparanase inhibitor heparastatin (SF4) suppresses infiltration of neutrophils and monocytes into inflamed dorsal air pouches

Sue, Mayumi; Higashi, Nobuaki; Shida, Hiroaki; Kogane, Yusuke; Nishimura, Yoshio; Adachi, Hayamitsu; Kołaczkowska, Elżbieta; Kepka, M.; Nakajima, Motowo; Irimura, Tatsuro

doi:10.1016/j.intimp.2016.03.017

Cited by 12 publications

(8 citation statements)

References 33 publications

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“…Furthermore, heparan sulfate’s role in the regulation of infiltration of neutrophils and monocytes has been established in a dorsal air pouch inflammation model. Here, it was demonstrated that the degradation of HS chains of basement membrane PGs enhances the extravasation of inflammatory cells [ 218 ]. Another example of PG involvement in the formation of a “permissive” tumor microenvironment is the action of perlecan, whose inflammation-mediated modifications have the role of being a “switch” between tumor permissive and prohibiting states [ 124 ].…”

Section: The Contribution Of Pgs To the Immunobiology Of Hormone-dmentioning

confidence: 99%

Proteoglycans in the Pathogenesis of Hormone-Dependent Cancers: Mediators and Effectors

Tzanakakis

Giatagana

Kuskov

et al. 2020

Cancers

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Hormone-dependent cancers exhibit high morbidity and mortality. In spite of advances in therapy, the treatment of hormone-dependent cancers remains an unmet health need. The tumor microenvironment (TME) exhibits unique characteristics that differ among various tumor types. It is composed of cancerous, non-cancerous, stromal, and immune cells that are surrounded and supported by components of the extracellular matrix (ECM). Therefore, the interactions among cancer cells, stromal cells, and components of the ECM determine cancer progression and response to therapy. Proteoglycans (PGs), hybrid molecules consisting of a protein core to which sulfated glycosaminoglycan chains are bound, are significant components of the ECM that are implicated in all phases of tumorigenesis. These molecules, secreted by both the stroma and cancer cells, are crucial signaling mediators that modulate the vital cellular pathways implicated in gene expression, phenotypic versatility, and response to therapy in specific tumor types. A plethora of deregulated signaling pathways contributes to the growth, dissemination, and angiogenesis of hormone-dependent cancers. Specific inputs from the endocrine and immune systems are some of the characteristics of hormone-dependent cancer pathogenesis. Importantly, the mechanisms involved in various aspects of cancer progression are executed in the ECM niche of the TME, and the PG components crucially mediate these processes. Here, we comprehensively discuss the mechanisms through which PGs affect the multifaceted aspects of hormone-dependent cancer development and progression, including cancer metastasis, angiogenesis, immunobiology, autophagy, and response to therapy.

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Section: The Contribution Of Pgs To the Immunobiology Of Hormone-dmentioning

confidence: 99%

Proteoglycans in the Pathogenesis of Hormone-Dependent Cancers: Mediators and Effectors

Tzanakakis

Giatagana

Kuskov

et al. 2020

Cancers

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“…According to this report, sepsis associated loss of the pulmonary glycocalyx and endothelial hyperpermeability were attenuated in heparanase-null mice and in mice treated with inhibitors of heparanase enzymatic activity [107]. Another study, utilizing a dorsal air pouch inflammation model demonstrated that heparastatin (an iminosugar-based inhibitor of heparanase) potentially suppresses extravasation of neutrophils and monocytes by impairing the degradation of basement membrane heparan sulfate [128]. On the other hand, several recent reports combining heparanase knock out approach and/or inhibitors with in vivo models of airway inflammation found no significant effect of the enzyme in neutrophil recruitment/entrapment in the lung vasculature [110,125].…”

Section: Heparanase In Inflammationmentioning

confidence: 99%

Heparanase regulation of cancer, autophagy and inflammation: new mechanisms and targets for therapy

et al. 2016

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Because of its impact on multiple biological pathways, heparanase has emerged as a major regulator of cancer, inflammation and other disease processes. Heparanase accomplishes this by degrading heparan sulfate which regulates the abundance and location of heparin-binding growth factors thereby influencing multiple signaling pathways that control gene expression, syndecan shedding and cell behavior. In addition, heparanase can act via non-enzymatic mechanisms that directly activate signaling at the cell surface. Clinical trials testing heparanase inhibitors as anti-cancer therapeutics are showing early signs of efficacy in patients further emphasizing the biological importance of this enzyme. This review focuses on recent developments in the field of heparanase regulation of cancer and inflammation, including the impact of heparanase on exosomes and autophagy, and novel mechanisms whereby heparanase regulates tumor metastasis, angiogenesis and chemoresistance. In addition, the ongoing development of heparanase inhibitors and their potential for treating cancer and inflammation are discussed.

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“…More work needs to be done to define and understand the effects of heparanase inhibitors on cells of the immune system. Heparanase inhibitors have been used as anti-inflammatory agents, and have been shown to impair lymphocyte trafficking (116, 117) and leukocyte function (46, 47, 61, 118). It is possible that in some tumor settings, heparanase inhibitors may inhibit leukocyte function, and consequently tip the balance away from tumor clearance and in favor of tumor progression.…”

Section: Heparanase Inhibitors and Leukocyte Functionmentioning

confidence: 99%

Leukocyte Heparanase: A Double-Edged Sword in Tumor Progression

2019

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Heparanase is a β-D-endoglucuronidase that cleaves heparan sulfate, a complex glycosaminoglycan found ubiquitously throughout mammalian cells and tissues. Heparanase has been strongly associated with important pathological processes including inflammatory disease and tumor metastasis, through its ability to promote various cellular functions such as cell migration, invasion, adhesion, and cytokine release. A number of cell types express heparanase including leukocytes, cells of the vasculature as well as tumor cells. However, the relative contribution of heparanase from these different cell sources to these processes is poorly defined. It is now well-established that the immune system plays a critical role in shaping tumor progression. Intriguingly, leukocyte-derived heparanase has been shown to either assist or impede tumor progression, depending on the setting. This review covers our current knowledge of heparanase in immune regulation of tumor progression, as well as the potential applications and implications of exploiting or inhibiting heparanase in cancer therapy.

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An iminosugar-based heparanase inhibitor heparastatin (SF4) suppresses infiltration of neutrophils and monocytes into inflamed dorsal air pouches

Cited by 12 publications

References 33 publications

Proteoglycans in the Pathogenesis of Hormone-Dependent Cancers: Mediators and Effectors

Proteoglycans in the Pathogenesis of Hormone-Dependent Cancers: Mediators and Effectors

Heparanase regulation of cancer, autophagy and inflammation: new mechanisms and targets for therapy

Leukocyte Heparanase: A Double-Edged Sword in Tumor Progression

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