Pleiotrophin is a potential colorectal cancer prognostic factor that promotes VEGF expression and induces angiogenesis in colorectal cancer

Kong, Ying; Bai, Pei-song; Kang, Nan; Sun, Huizhen; Chen, Nanzheng; Qi, Xu

doi:10.1007/s00384-011-1344-z

Cited by 38 publications

(42 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In favour of a stimulatory effect of PTN on in vivo angiogenesis are also our additional data showing that exogenously added PTN onto the chicken embryo CAM increases the mRNA levels of vascular endothelial growth factor (VEGF) isoforms 165 and 190, as well as activates metalloproteinase 2 (Additional file 4). These data are in line with a recent work showing that PTN promotes VEGF expression and cooperates with VEGF in promoting colorectal cancer angiogenesis [21]. Interestingly, although PTN seems to affect the number of angiogenic blood vessels, it did not affect lymphatic endothelial cells' marker PROX-1 expression, suggesting that PTN does not affect lymphatic vessel density, in line with data on colorectal cancer showing that lymphatic microvessel density does not correlate with PTN expression [21].…”

Section: Discussionsupporting

confidence: 90%

Pleiotrophin expression and role in physiological angiogenesis in vivo: potential involvement of nucleolin

et al. 2012

View full text Add to dashboard Cite

BackgroundPleiotrophin (PTN) is a heparin-binding growth factor with significant role(s) in tumour growth and angiogenesis. Although implication of endogenous PTN has been studied in several in vivo models of tumour angiogenesis, its role in physiological angiogenesis has not been addressed. In the present work, we studied expression and functional significance of endogenous PTN during angiogenesis in the chicken embryo chorioallantoic membrane (CAM).MethodsUsing molecular, cellular and biochemical assays, we studied the expression pattern of PTN in CAM and human endothelial cells and its possible interaction with nucleolin (NCL). CAM cells were transfected with a pCDNA3.1 vector, empty (PC) or containing full length cDNA for PTN in antisense orientation (AS-PTN). Angiogenesis was estimated by measuring total vessel length. In vitro, human endothelial cells migration was studied by using a transwell assay, and down-regulation of NCL was performed by using a proper siRNA.ResultsEndogenous PTN mRNA and protein levels, as well as protein levels of its receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ) were maximal at early stages, when CAM angiogenesis is active. Application of AS-PTN onto CAM at days of active angiogenesis was not toxic to the tissue and led to dose-dependent decreased expression of endogenous PTN, ERK1/2 activity and angiogenesis. Interestingly, endogenous PTN was also immunolocalized at the endothelial cell nucleus, possibly through interaction with NCL, a protein that has a significant role in the nuclear translocation of many proteins. Down-regulation of NCL by siRNA in human endothelial cells significantly decreased nuclear PTN, verifying this hypothesis. Moreover, it led to abolishment of PTN-induced endothelial cell migration, suggesting, for the first time, that PTN-NCL interaction has a functional significance.ConclusionsExpression of endogenous PTN correlates with and seems to be involved in angiogenesis of the chicken embryo CAM. Our data suggest that NCL may have a role, increasing the number of growth factors whose angiogenic/tumorigenic activities are mediated by NCL.

show abstract

Section: Discussionsupporting

confidence: 90%

Pleiotrophin expression and role in physiological angiogenesis in vivo: potential involvement of nucleolin

et al. 2012

View full text Add to dashboard Cite

show abstract

“…For example, PTN up-regulates the mRNA levels of VEGF isoforms 165 and 190, as well as activates metalloproteinase 2 in the chick embryo CAM [78] and promotes VEGF expression and cooperates with VEGF in promoting colorectal cancer angiogenesis [66]. PTN induces proliferation of human peripheral blood mononuclear cells [67] and increases the mRNA expression of the VEGF receptor 1 in endothelial cell cultures [62].…”

Section: Ptn and Angiogenesismentioning

confidence: 99%

The role of pleiotrophin in bone repair

Lamprou

Kaspiris

Panagiotopoulos

et al. 2014

Injury

View full text Add to dashboard Cite

“…Ptn is a mitogen for endothelial cells, epithelial cells and fibroblast cells [20, 39, 45], and is expressed in multiple cancers, including breast, prostate, ovarian, lung, melanoma, head and neck, glioblastoma, neuroblastoma, pancreatic carcinoma and choriocarcinoma [13]. The cytokine is a prognostic factor for colorectal cancer [46] and a protooncogene associated with tumor angiogenesis and tumor cell proliferation [47]. In vitro functional assays, including tube formation, migration and sprouting of endothelial cells from various organs, confirm a direct angiogenic activity of Ptn [21, 48].…”

Section: Discussionmentioning

confidence: 99%

“…For example, Ptn induces VEGF expression to promote angiogenesis [21, 46, 57]. On the other hand, Ptn directly binds to VEGF and inhibits VEGF-induced endothelial proliferation and tube formation [58].…”

Section: Discussionmentioning

confidence: 99%

Pathogenic role and therapeutic potential of pleiotrophin in mouse models of ocular vascular disease

et al. 2017

View full text Add to dashboard Cite

Angiogenic factors play an important role in the pathogenesis of diabetic retinopathy (DR), neovascular age-related macular degeneration (nAMD) and retinopathy of prematurity (ROP). Pleiotrophin, a well-known angiogenic factor, was recently reported to be upregulated in the vitreous fluid of patients with proliferative DR (PDR). However, its pathogenic role and therapeutic potential in ocular vascular diseases have not been defined in vivo. Here using corneal pocket assays, we demonstrated that pleiotrophin induced angiogenesis in vivo. To investigate the pathological role of pleiotrophin we used neutralizing antibody to block its function in multiple in vivo models of ocular vascular diseases. In a mouse model of DR, intravitreal injection of pleiotrophin-neutralizing antibody alleviated diabetic retinal vascular leakage. In a mouse model of oxygen-induced retinopathy (OIR), which is a surrogate model of ROP and PDR, we demonstrated that intravitreal injection of anti-pleiotrophin antibody prevented OIR-induced pathological retinal neovascularization and aberrant vessel tufts. Finally, pleiotrophin-neutralizing antibody ameliorated laser-induced choroidal neovascularization, a mouse model of nAMD, suggesting that pleiotrophin is involved in choroidal vascular disease. These findings suggest that pleiotrophin plays an important role in the pathogenesis of DR with retinal vascular leakage, ROP with retinal neovascularization and nAMD with choroidal neovascularization. The results also support pleiotrophin as a promising target for anti-angiogenic therapy.

show abstract

Pleiotrophin is a potential colorectal cancer prognostic factor that promotes VEGF expression and induces angiogenesis in colorectal cancer

Cited by 38 publications

References 27 publications

Pleiotrophin expression and role in physiological angiogenesis in vivo: potential involvement of nucleolin

Pleiotrophin expression and role in physiological angiogenesis in vivo: potential involvement of nucleolin

The role of pleiotrophin in bone repair

Pathogenic role and therapeutic potential of pleiotrophin in mouse models of ocular vascular disease

Contact Info

Product

Resources

About