PLAP-1/Asporin Positively Regulates FGF-2 Activity

Awata, T.; Yamada, Satoru; Tsushima, K.; Sakashita, Hiromi; Yamaba, S.; Kajikawa, Tetsuhiro; Yamashita, Masaru; Takedachi, Masahide; Yanagita, Manabu; Kitamura, Masahiro; Murakami, Shinya

doi:10.1177/0022034515598507

Cited by 30 publications

(33 citation statements)

References 38 publications

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“…Asporin negatively regulates TGFβ and this leads to an increase in cell proliferation and a decrease in apoptosis. More recently it has been shown that ASPN regulates TLR2- and TLR4-induced inflammatory responses (Yamaba et al , 2015) and also positively regulates FGF2 activity (Awata et al , 2015). FGF2 is increased in prostate cancer compared to normal prostate tissue, and increased FGF2 is localised to the tumour stroma.…”

Section: Discussionmentioning

confidence: 99%

“…It regulates BMP2, TGFβ and FGF2 activity through direct and indirect interactions (Kizawa et al , 2005; Yamada et al , 2007; Tomoeda et al , 2008; Awata et al , 2015) and also binds type II collagen (Kou et al , 2010). ASPN has been shown to play a role in invasion in breast cancer cells (Simkova et al , 2016) and control the invasion of tumour cells and CAFs in scirrhous type gastric cancer (Satoyoshi et al , 2014), both in vitro and in vivo via the CD44-Rac1 pathway (Satoyoshi et al , 2014).…”

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Asporin is a stromally expressed marker associated with prostate cancer progression

et al. 2017

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Background:Prostate cancer shows considerable heterogeneity in disease progression and we propose that markers expressed in tumour stroma may be reliable predictors of aggressive tumour subtypes.Methods:We have used Kaplan–Meier, univariate and multivariate analysis to correlate the expression of Asporin (ASPN) mRNA and protein with prostate cancer progression in independent cohorts. We used immunohistochemistry and H scoring to document stromal localisation of ASPN in a tissue microarray and mouse prostate cancer model, and correlated expression with reactive stroma, defined using Masson Trichrome staining. We used cell cultures of primary prostate cancer fibroblasts treated with serum-free conditioned media from prostate cancer cell lines to examine regulation of ASPN mRNA in tumour stromal cells.Results:We observed increased expression of ASPN mRNA in a data set derived from benign vs tumour microdissected tissue, and a correlation with biochemical recurrence using Kaplan–Meier and Cox proportional hazard analysis. ASPN protein localised to tumour stroma and elevated expression of ASPN was correlated with decreased time to biochemical recurrence, in a cohort of 326 patients with a median follow up of 9.6 years. Univariate and multivariate analysis demonstrated that ASPN was correlated with progression, as were Gleason score, and clinical stage. Additionally, ASPN expression correlated with the presence of reactive stroma, suggesting that it may be a stromal marker expressed in response to the presence of tumour cells and particularly with aggressive tumour subtypes. We observed expression of ASPN in the stroma of tumours induced by p53 inhibition in a mouse model of prostate cancer, and correlation with neuroendocrine marker expression. Finally, we demonstrated that ASPN transcript expression in normal and cancer fibroblasts was regulated by conditioned media derived from the PC3, but not LNCaP, prostate cancer cell lines.Conclusions:Our results suggest that ASPN is a stromally expressed biomarker that correlates with disease progression, and is observed in reactive stroma. ASPN expression in stroma may be part of a stromal response to aggressive tumour subtypes.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Asporin is a stromally expressed marker associated with prostate cancer progression

et al. 2017

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“…In gastric cancer, asporin contributes to metastasis through EGFR and ERK-CD44/MMP-2 pathways [9]. Awata et al demonstrated that asporin could directly bind to FGF-2 and form an FGF-2–FGFR1 complex [18]. Phosphorylated EGFR recruited multiple Src homology 2 domains and activated their downstreaming signaling pathways [19].…”

Section: Discussionmentioning

confidence: 99%

Asporin enhances colorectal cancer metastasis through activating the EGFR/Src/cortactin signaling pathway

Jing

Cheng

et al. 2016

Oncotarget

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Asporin has been implicated as an oncogene in various types of human cancers; however, the roles of asporin in the development and progression of colorectal cancer (CRC) have not yet been determined. With clinical samples, we found that asporin was highly expressed in CRC tissues compared to adjacent normal tissues and the asporin expression levels were significantly associated with lymph node metastasis status and TNM stage of the patients. Through knockdown of asporin in CRC cell lines RKO and SW620 or overexpression of asporin in cell lines HT-29 and LoVo, we found that asporin could enhance wound healing, migration and invasion abilities of the CRC cells. Further more, with the human umbilical vein endothelial cells (HUVECs) tube formation assays and the xenograft model, we found that asporin promoted the tumor growth through stimulating the VEGF signaling pathway. The portal vein injection models suggested that asporin overexpression stimulated the liver metastasis of HT29 cell line, while asporin knockdown inhibited the liver metastasis of RKO cell line. In addition, asporin was found to augment the phosphorylation of EGFR/Src/cortactin signaling pathway, which might be contributed to the biological functions of asporin in CRC metastasis. These results suggested that asporin promoted the tumor growth and metastasis of CRC, and it could be a potential therapeutic target for CRC patients in future.

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“…It has also been demonstrated that PLAP-1, an extracellular matrix protein that is mainly expressed in the periodontal ligament, regulates BMP-2 and FGF-2 activity through direct interaction, and TGF-b through indirect interaction (Awata et al 2015). The functions of the bioactive molecule FGF-2, for instance, are regulated by PLAP-1 through the formation of the FGF-2-FGFR1 complex via direct binding (Awata et al 2015). The functions of the bioactive molecule FGF-2, for instance, are regulated by PLAP-1 through the formation of the FGF-2-FGFR1 complex via direct binding (Awata et al 2015).…”

Section: The Role Of Bioactive Molecules In Physiological and Patholomentioning

confidence: 99%

Disclosing the physiology of pulp tissue for vital pulp therapy

2018

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The discovery that dentine is a reservoir of bioactive molecules that can be recruited on demand has attracted efforts to develop new protocols and materials for vital pulp therapy (VPT). The noncollagenous proteins (NCPs) present in the dentine extracellular matrix (ECM) include growth factors (TGF-β1, BMP-7, FGF-2, IGF-1 and IGF-2, NGF and GDNF), extracellular matrix molecules (DSP, DPP, BSP, DMP-1 and DSPP) and both anti-inflammatory and pro-inflammatory chemokines and cytokines (TNF-α, IL-1, IL-6 and IL-10). Molecules such as DSP and DPP are mainly expressed by odontoblasts, and they are cleaved products from dentine sialophosphoprotein (DSPP). Some molecules, such as TGF-β1, specifically interact with decorin/biglycan in dentine. Although TGF-β1 increases the expression and secretion of NGF in human pulp cells, NGF induces mineralization and increases the expression of DSPP and DMP-1. Furthermore, GDNF may act as a cell survival factor and mitogen during tooth injury and repair. Pulp capping materials, such as MTA and calcium hydroxide, can solubilize bioactive dentine molecules (TGF-β1, NGF and GDNF) that stimulate tertiary dentinogenesis. The binding of these signalling molecules leads to activation of several signalling transduction pathways involved in dentinogenesis, odontoblast differentiation and inflammatory responses, such as the p38 MAPK, NF-kβ and Wnt/β-catenin signalling pathways. Understanding the cascade of cellular and molecular events underlying the repair and regeneration processes provides a reasonable new approach to VPT through a targeted interaction between tooth tissue and bioactive molecules.

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PLAP-1/Asporin Positively Regulates FGF-2 Activity

Cited by 30 publications

References 38 publications

Asporin is a stromally expressed marker associated with prostate cancer progression

Asporin is a stromally expressed marker associated with prostate cancer progression

Asporin enhances colorectal cancer metastasis through activating the EGFR/Src/cortactin signaling pathway

Disclosing the physiology of pulp tissue for vital pulp therapy

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