Hyaluronan Regulation of Endothelial Barrier Function in Cancer

Singleton, Patrick A.

doi:10.1016/b978-0-12-800092-2.00007-1

Cited by 59 publications

(54 citation statements)

References 111 publications

(159 reference statements)

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“…Thus, the angiogenic properties of LMW-HA and HMW-HA may vary depending on the composition of the microenvironment. Nevertheless, a high HA expression was shown to correlate with increased angiogenesis and poor prognosis [212] and the assessment of this molecule may represent an important mean for the development of new prognostic tools [199]. …”

Section: Hyaluronan: Not Only a Mere Gluementioning

confidence: 99%

Extracellular Matrix, a Hard Player in Angiogenesis

Mongiat

Andreuzzi

Tarticchio

et al. 2016

IJMS

165

133

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The extracellular matrix (ECM) is a complex network of proteins, glycoproteins, proteoglycans, and polysaccharides. Through multiple interactions with each other and the cell surface receptors, not only the ECM determines the physical and mechanical properties of the tissues, but also profoundly influences cell behavior and many physiological and pathological processes. One of the functions that have been extensively explored is its impingement on angiogenesis. The strong impact of the ECM in this context is both direct and indirect by virtue of its ability to interact and/or store several growth factors and cytokines. The aim of this review is to provide some examples of the complex molecular mechanisms that are elicited by these molecules in promoting or weakening the angiogenic processes. The scenario is intricate, since matrix remodeling often generates fragments displaying opposite effects compared to those exerted by the whole molecules. Thus, the balance will tilt towards angiogenesis or angiostasis depending on the relative expression of pro- or anti-angiogenetic molecules/fragments composing the matrix of a given tissue. One of the vital aspects of this field of research is that, for its endogenous nature, the ECM can be viewed as a reservoir to draw from for the development of new more efficacious therapies to treat angiogenesis-dependent pathologies.

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Section: Hyaluronan: Not Only a Mere Gluementioning

confidence: 99%

Extracellular Matrix, a Hard Player in Angiogenesis

Mongiat

Andreuzzi

Tarticchio

et al. 2016

IJMS

165

133

View full text Add to dashboard Cite

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“…Besides "true" PGs, hyaluronan (HA), a non-sulfated glycosaminoglycan that is never covalently linked to a protein core, is capable of evoking a danger signal in response to injury following partial enzymatic cleavage by hyaluronidases (23). The resulting low molecular weight (LMW)-HA fragments accumulate and stimulate TLR2/4 and inflammatory gene expression, thereby promoting angiogenesis and cancer metastasis (7,23,24). Furthermore, active heparan sulfate (HS) fragments generated by heparanase-1 from extracellular barriers (25) and HS proteoglycan sources, such as the basement membrane perlecan (26), the cell surface syndecans (27), and glypicans (28), serve as TLR4-interacting DAMPs (29,30) (Fig.…”

Section: Damps Derived From the Extracellular Matrix (Ecm)mentioning

confidence: 99%

Complexity of Danger: The Diverse Nature of Damage-associated Molecular Patterns

Schaefer

2014

Journal of Biological Chemistry

519

467

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In reply to internal or external danger stimuli, the body orchestrates an inflammatory response. The endogenous triggers of this process are the damage-associated molecular patterns (DAMPs). DAMPs represent a heterogeneous group of molecules that draw their origin either from inside the various compartments of the cell or from the extracellular space. Following interaction with pattern recognition receptors in crosstalk with various non-immune receptors, DAMPs determine the downstream signaling outcome of septic and aseptic inflammatory responses. In this review, the diverse nature, structural characteristics, and signaling pathways elicited by DAMPs will be critically evaluated.

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“…19 Studies have indicated that impairment of blood vascular barrier could be mediated by LMW-HA and an accelerating vascular metastasis of cancer cells was followed. 20,21 To date, there are no reports regarding how LMW-HA modulates lymphatic endothelial cell junctions or facilitates cancer cell metastasis through lymph vessels. As lymphatic vascular endothelial cells are similar to blood vessels in terms of their proliferation behavior and HA receptor expression patterns, it is reasonable to assume that LMW-HA regulates lymphatic endothelial intercellular adhesion by binding to lymphatic endothelial hyaluronan receptor-1 (LYVE-1) and thus accelerates tumor cell migration into the lumen of lymphatic vessels.…”

Section: Introductionmentioning

confidence: 99%

Low-molecular-weight hyaluronan (LMW-HA) accelerates lymph node metastasis of melanoma cells by inducing disruption of lymphatic intercellular adhesion

Cao

Liu

et al. 2016

OncoImmunology

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Endothelial integrity defects initiate lymphatic metastasis of tumor cells. Low-molecular-weight hyaluronan (LMW-HA) derived from plasma and interstitial fluid was reported to be associated with tumor lymphatic metastasis. In addition, LMW-HA was proved to disrupt lymphatic vessel endothelium integrity, thus promoting lymphatic metastasis of tumor cells. Until now, there are few reports on how LMW-HA modulates lymphatic endothelial cells adhesion junctions and affects cancer cells metastasizing into lymph vessels. The aim of our study is to unravel the novel mechanism of LMW-HA in mediating tumor lymphatic metastasis. Here, we employed a melanoma metastasis model to investigate whether LMW-HA facilitates tumor cells transferring from foci to remote lymph nodes by disrupting the lymphatic endothelial integrity. Our data indicate that LMW-HA significantly induces metastasis of melanoma cells to lymph nodes and accelerates interstitial-lymphatic flow in vivo. Further experiments show that increased migration of melanoma cells across human dermal lymphatic endothelial cell (HDLEC) monolayers is accompanied by impaired lymphatic endothelial barrier function and increased permeability. The mechanism study reveals that VE-cadherin-b-catenin pathway and relevant signals are involved in modulating the interactions between endothelial cells and that a significant inhibition of lymphatic endothelium disruption is observed when antibodies to the LMW-HA receptor (LYVE-1) are present. Thus, our findings demonstrate a disruptive effect of LMW-HA on lymphatic endothelium continuity which leads to a promotion on melanoma lymphatic metastasis and also suggest a cellular signaling mechanism associated with VE-cadherin-mediated lymphatic intercellular junctions.

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Hyaluronan Regulation of Endothelial Barrier Function in Cancer

Cited by 59 publications

References 111 publications

Extracellular Matrix, a Hard Player in Angiogenesis

Extracellular Matrix, a Hard Player in Angiogenesis

Complexity of Danger: The Diverse Nature of Damage-associated Molecular Patterns

Low-molecular-weight hyaluronan (LMW-HA) accelerates lymph node metastasis of melanoma cells by inducing disruption of lymphatic intercellular adhesion

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