Gastric Invasion of the Intraductal Papillary Mucinous Tumor

Hs, Kim; Yoo, K-S; Han, DS

doi:10.1016/s2212-0971(13)70070-0

Cited by 2 publications

(3 citation statements)

References 2 publications

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“…Mucins are immunologically active through the binding of their sugar residues to lectin-like proteins on the surface of immune cells. , The muc2 mucins found in the gut can imprint dendritic cells tolerance and, in contrast, can activate nonstimulated dendritic cells in a concentration-dependent manner . In mucinous carcinomas, secreted mucins surround the tumors protecting them from cancer drugs and immune cell infiltration both physically and biochemically . Inoue et al reported that bovine submaxillary mucins supplemented in cell culture medium could activate IL1b expression in macrophages derived from the human THP-1 monocyte cell line (THP-1-M0) in a sialic acid-dependent manner …”

Section: Introductionmentioning

confidence: 99%

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Glyco-Modification of Mucin Hydrogels to Investigate Their Immune Activity

Yan

Hjorth

Winkeljann

et al. 2020

ACS Appl. Mater. Interfaces

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Mucins are multifunctional glycosylated proteins that are increasingly investigated as building blocks of novel biomaterials. An attractive feature is their ability to modulate the immune response, in part by engaging with sialic acid binding receptors on immune cells. Once assembled into hydrogels, bovine submaxillary mucins (Muc gels) were shown to modulate the recruitment and activation of immune cells and avoid fibrous encapsulation in vivo. However, nothing is known about the early immune response to Muc gels. This study characterizes the response of macrophages, important orchestrators of the material-mediated immune response, over the first 7 days in contact with Muc gels. The role of mucin-bound sialic acid sugar residues was investigated by first enzymatically cleaving the sugar and then assembling the mucin variants into covalently cross-linked hydrogels with rheological and surface nanomechanical properties similar to nonmodified Muc gels. Results with THP-1 and human primary peripheral blood monocytes derived macrophages showed that Muc gels transiently activate the expression of both pro-inflammatory and anti-inflammatory cytokines and cell surface markers, for most makers with a maximum on the first day and loss of the effect after 7 days. The activation was sialic acid-dependent for a majority of the markers followed. The pattern of gene expression, protein expression, and functional measurements did not strictly correspond to M1 or M2 macrophage phenotypes. This study highlights the complex early events in macrophage activation in contact with mucin materials and the importance of sialic acid residues in such a response. The enzymatic glyco-modulation of Muc gels appears as a useful tool to help understand the biological functions of specific glycans on mucins which can further inform on their use in various biomedical applications.

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Section: Introductionmentioning

confidence: 99%

“…17 In mucinous carcinomas, secreted mucins surround the tumors protecting them from cancer drugs and immune cell infiltration both physically and biochemically. 18 Inoue et al…”

Section: ■ Introductionmentioning

confidence: 99%

Glyco-Modification of Mucin Hydrogels to Investigate Their Immune Activity

Yan

Hjorth

Winkeljann

et al. 2020

ACS Appl. Mater. Interfaces

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show abstract

“…In many types of tumors, transmembrane mucins are altered in their expression level 19 and glycosylation pattern marked by a general reduction of glycosylation 20 and truncation of O-linked glycans 21 . In mucinous carcinomas, secreted mucins surround the tumors protecting them from cancer drugs and immune cell infiltration both physically and biochemically 22 . Mucins are immunologically active through the binding of their sugar residues to lectin-like proteins on the surface of immune cells 18,23,24 .…”

Section: Introductionmentioning

confidence: 99%

Mucin hydrogel glyco-modulation to investigate immune activity of mucin glycans

Yan

Hjorth

Winkeljann

et al. 2019

Preprint

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Mucins are multifunctional glycosylated proteins that are increasingly investigated as building blocks of novel biomaterials. Once assembled into hydrogels (Muc gels), mucins were shown to modulate the recruitment and activation of immune cells and avoid fibrous encapsulation in vivo.However, nothing is known about the early immune response to Muc gels. This study characterizes the response of macrophages, important orchestrators of the material-mediated immune response, over the first 7 days in contact with Muc gels. The role of mucin-bound sialic acid sugar residues was investigated by first enzymatically cleaving the sugar, then assembling the mucin variants into covalently crosslinked hydrogels with rheological and surface nanomechanical properties similar to non-modified Muc gels. Results with THP1 and human primary peripheral blood monocytesderived macrophages were strikingly consistent and showed that Muc gels transiently activate the expression of both pro-inflammatory and anti-inflammatory cytokines and cell surface markers, with a maximum on the first day and loss of the effect after 7 days. The activation was sialic aciddependent for a majority of the markers followed. The pattern of gene expression, protein expression, and functional measurements did not strictly correspond to M1 or M2 macrophage phenotypes. This study highlights the complex early events in macrophage activation in contact with mucin materials and the importance of sialic acid residues in such a response. The enzymatic glyco-modulation of Muc gels appears as a useful tool to help understand the biological functions of specific glycans on mucins which can further inform on their use in various biomedical applications.

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Gastric Invasion of the Intraductal Papillary Mucinous Tumor

Cited by 2 publications

References 2 publications

Glyco-Modification of Mucin Hydrogels to Investigate Their Immune Activity

Glyco-Modification of Mucin Hydrogels to Investigate Their Immune Activity

Mucin hydrogel glyco-modulation to investigate immune activity of mucin glycans

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