Low Concentration of S100A8/9 Promotes Angiogenesis-Related Activity of Vascular Endothelial Cells: Bridges among Inflammation, Angiogenesis, and Tumorigenesis?

Li, Changyou; Liu, Siyuan; Jia, Changkai; Yang, Lingling; Song, Zicheng

doi:10.1155/2012/248574

Cited by 40 publications

(44 citation statements)

References 41 publications

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“…It has been demonstrated that S100A8 is secreted by myeloid cells (25) and that prerequisite for its secretion is the contact of myeloid cells with an inflamed endothelium (26) via heparin sulfate proteoglycans (27). Whereas low concentrations of S100A8 (10 ∼ 25 μg/mL) have shown to promote migration and proliferation of endothelial cells (28) and increased vascular permeability (25), higher concentrations of S100A8 (200 μg/mL) have shown to result in endothelial apoptosis (29). Other mechanisms including S100A8/9-mediated increase in the binding capacity of CD11b/CD18 myeloid cells onto the endothelium (30) or nitric oxide production in myeloid cells (31) leading to vasodilation may also participate in S100A8 myeloid cell-driven angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional activation of hypoxia-inducible factor-1 (HIF-1) in myeloid cells promotes angiogenesis through VEGF and S100A8

Ahn

Seita

Hong

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Emerging evidence indicates that myeloid cells are essential for promoting new blood vessel formation by secreting various angiogenic factors. Given that hypoxia-inducible factor (HIF) is a critical regulator for angiogenesis, we questioned whether HIF in myeloid cells also plays a role in promoting angiogenesis. To address this question, we generated a unique strain of myeloid-specific knockout mice targeting HIF pathways using human S100A8 as a myeloid-specific promoter. We observed that mutant mice where HIF-1 is transcriptionally activated in myeloid cells (by deletion of the von HippelLindau gene) resulted in erythema, enhanced neovascularization in matrigel plugs, and increased production of vascular endothelial growth factor (VEGF) in the bone marrow, all of which were completely abrogated by either genetic or pharmacological inactivation of HIF-1. We further found that monocytes were the major effector producing VEGF and S100A8 proteins driving neovascularization in matrigel. Moreover, by using a mouse model of hindlimb ischemia we observed significantly improved blood flow in mice intramuscularly injected with HIF-1-activated monocytes. This study therefore demonstrates that HIF-1 activation in myeloid cells promotes angiogenesis through VEGF and S100A8 and that this may become an attractive therapeutic strategy to treat diseases with vascular defects.

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Section: Discussionmentioning

confidence: 99%

Transcriptional activation of hypoxia-inducible factor-1 (HIF-1) in myeloid cells promotes angiogenesis through VEGF and S100A8

Ahn

Seita

Hong

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Low concentrations of S100A8 and S100A9 promote proliferation, migration, and angiogenesis, whereas high concentrations of S100A9 exert a proapoptotic effect on vascular endothelial cells (Li et al, 2012). Stable expression of calprotectin subunits in HeLa-KB cells suppresses carcinoma growth in vivo and in vitro by restoring the G2/M cell cycle checkpoint (Chen et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Effect of calprotectin subunit S100A9 on the expression and methylation of OCLN in human melanoma cell line A-375

Najafi¹,

Alizadeh²,

Azad³

et al. 2017

Turk J Biol

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Increased levels of calprotectin subunits S100A8 and S100A9 have been detected in human cancers. Melanoma is the most aggressive type of skin cancer, and its treatment is challenging because of its brain metastasis. OCLN encodes occludin, which plays a major role in the formation and regulation of tight junctions. The aim of this study was to evaluate the methylation status of the OCLN promoter and its expression in A-375 melanoma cells treated with or without various concentrations of S100A9 for 24, 48, and 72 h. Total RNA was extracted, and synthesized cDNA was assessed by performing real-time PCR. MSP-PCR was performed after treatment with bisulfite. Recombinant S100A9 inhibited the proliferation of the A-375 cell line and the expression of the OCLN gene was downregulated in a time-and concentration-dependent manner. Results of MSP-PCR showed that the OCLN gene promoter in a human melanoma cell line (A-375) was semimethylated.

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“…Em contrapartida aos efeitos descritos acima, as proteínas S100A8/A9, em baixas concentrações (<20µg/mL), promovem proliferação de células tumorais e de células endoteliais por meio de diferentes mecanismos (LI et al, 2012;SRIKRISHNA, 2012). Assim, 100pg/mL e 1ng/mL de S100A8 e S100A9, respectivamente, promovem a migração celular de carcinoma de pulmão e de células B16 em melanoma em câmaras Boyden.…”

Section: Figura 1 -Organização Da Actinaunclassified

“…Assim, em um estudo realizado com linhagem de célula endotelial vascular de cordão umbilical humano (HUVEC) foi demonstrado que estas duas proteínas sozinhas ou em combinação, em baixas concentrações, promoveram proliferação, migração celular e formação de estruturas tubo-like em Matrigel (LI et al, 2012). Ainda, quando combinadas, as proteínas S100A8 e S100A9 promovem efeito aditivo, sugerindo que as duas proteínas agem sinergicamente.…”

Section: Figura 1 -Organização Da Actinaunclassified

“…Ainda, quando combinadas, as proteínas S100A8 e S100A9 promovem efeito aditivo, sugerindo que as duas proteínas agem sinergicamente. Esses dados sugerem que as proteínas S100A8/A9, as quais podem ser provenientes tanto de células do infiltrado inflamatório, quanto de células tumorais, desempenham papel importante na inter-relação entre inflamação, angiogênese e tumorigênese (LI et al, 2012).…”

Section: Figura 1 -Organização Da Actinaunclassified

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<b>O C-terminal da proteína S100A9 murina modula os eventos envolvidos na angiogênese e na progressão tumoral em modelos <i>in vitro</i></b>

Moraes¹

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RESUMOMORAES, N. F. O C-terminal da proteína S100A9 murina modula os eventos envolvidos na angiogênese e na progressão tumoral em modelos in vitro. [The C-terminus of the murine protein S100A9 modulates the events involved in angiogenesis and tumor progression using in vitro models.]. 2015. 81 f. Dissertação (Mestrado em Ciências) -Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, 2015.As proteínas S100A8/A9 são expressas em diferentes tipos celulares e quando sozinhas ou complexadas e em baixas concentrações, promoveram proliferação, migração celular e formação de estruturas capilares. Por outro lado, quando em altas concentrações, esse complexo inibe o crescimento de diversos tipos de células tumorais murinas e humanas.Ainda, tanto a proteína S100A9 humana, quanto um peptídeo sintético idêntico a porção Cterminal da proteína S100A9 murina (pS100A9m) The S100A8/A9 proteins are expressed in different cell types and alone or when complexed, and at low concentrations promoted proliferation, cell migration and formation of capillary structures. On the other hand, at higher concentrations, this compound inhibits the growth of many types of murine and human tumor cells. Moreover, both human S100A9 protein and a synthetic peptide identical to the C-terminal portion of murine S100A9 (mS100A9p) present antinociceptive and immunomodulatory effects. Despite these evidences, the effect of mS100A9p on angiogenesis and tumorigenesis has not been investigated. Therefore, the aim of this study was to investigate the in vitro effect of mS100A9p on crucial events involved in angiogenesis and tumor development. For this, in order to evaluate the effect of mS100A9p on angiogenesis was used the murine endothelial cell line derived from thymus hemangioma (tEnd.1) for proliferation assays, endothelial cell migration in the presence of culture medium (scratch wound healing and chemotaxis assays) or in conditioned medium prevenient from LLC WRC256 tumor cells (chemotaxis assays), adhesion assay (on extracellular matrix components, such as type I collagen, fibronectin and laminin) and tube like-structure formation in 3D matrix. For the analyzes of the effect of mS100A9p on tumor cells, the cell line LLC WRC256 was used to perform functional assays such as proliferation, migration (scratch wound healing model) and adhesion (on components of the extracellular matrix). The results showed that the mS100A9p inhibits the proliferation, migration and adhesion of endothelial cells to the matrix components and consequently the formation of capillary structures in 3D matrix. Regarding LLC WRC256 tumor cells, it was observed again the inhibitory action of the mS100A9p on proliferation and migration events. In relation to cellular adhesion, this peptide increased this parameter of tumor cells on type I collagen and fibronectin. However mS100A9p inhibited the adhesion of these cells on laminin. In conclusion, the data obtained show that the mS100A9p inhibits in vitro crucial events involved in angiogenesis and tum...

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Low Concentration of S100A8/9 Promotes Angiogenesis-Related Activity of Vascular Endothelial Cells: Bridges among Inflammation, Angiogenesis, and Tumorigenesis?

Cited by 40 publications

References 41 publications

Transcriptional activation of hypoxia-inducible factor-1 (HIF-1) in myeloid cells promotes angiogenesis through VEGF and S100A8

Transcriptional activation of hypoxia-inducible factor-1 (HIF-1) in myeloid cells promotes angiogenesis through VEGF and S100A8

Effect of calprotectin subunit S100A9 on the expression and methylation of OCLN in human melanoma cell line A-375

<b>O C-terminal da proteína S100A9 murina modula os eventos envolvidos na angiogênese e na progressão tumoral em modelos <i>in vitro</i></b>

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