Glioblastoma-secreted factors induce IGFBP7 and angiogenesis by modulating Smad-2-dependent TGF-β signaling

Pen, Ally; Moreno, María; Durocher, Yves; Deb-Rinker, Paromita; Stanimirovic, Danica

doi:10.1038/onc.2008.287

Cited by 99 publications

(86 citation statements)

References 65 publications

(76 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…IGFBP7 has been implicated in multiple biological processes including angiogenesis, tumor suppression, and senescence, mainly as a growth suppressor, and a role in G 1 cell-cycle arrest has been implicated (3,7,44,54,59,69). TIMP-2 has been implicated positively in kidney pathologies including cancer, glomerular disease, fibrosis, and tubuleinterstitial injury, in a matrix metalloproteinase (MMP)-dependent manner (16,29,45,71).…”

Section: Discussionmentioning

confidence: 99%

Insulin-like growth factor binding protein 7 and tissue inhibitor of metalloproteinases-2: differential expression and secretion in human kidney tubule cells

Emlet

Pastor-Soler

Marciszyn

et al. 2017

American Journal of Physiology-Renal Physiology

107

View full text Add to dashboard Cite

We have characterized the expression and secretion of the acute kidney injury (AKI) biomarkers insulin-like growth factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) in human kidney epithelial cells in primary cell culture and tissue. We established cell culture model systems of primary kidney cells of proximal and distal tubule origin and observed that both proteins are indeed expressed and secreted in both tubule cell types in vitro. However, TIMP-2 is both expressed and secreted preferentially by cells of distal tubule origin, while IGFBP7 is equally expressed across tubule cell types yet preferentially secreted by cells of proximal tubule origin. In human kidney tissue, strong staining of IGFBP7 was seen in the luminal brush-border region of a subset of proximal tubule cells, and TIMP-2 stained intracellularly in distal tubules. Additionally, while some tubular colocalization of both biomarkers was identified with the injury markers kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin, both biomarkers could also be seen alone, suggesting the possibility for differential mechanistic and/or temporal profiles of regulation of these early AKI biomarkers from known markers of injury. Last, an in vitro model of ischemia-reperfusion demonstrated enhancement of secretion of both markers early after reperfusion. This work provides a rationale for further investigation of these markers for their potential role in the pathogenesis of acute kidney injury.

show abstract

Section: Discussionmentioning

confidence: 99%

Insulin-like growth factor binding protein 7 and tissue inhibitor of metalloproteinases-2: differential expression and secretion in human kidney tubule cells

Emlet

Pastor-Soler

Marciszyn

et al. 2017

American Journal of Physiology-Renal Physiology

107

View full text Add to dashboard Cite

show abstract

“…12 IGFBP7 accumulates in vessels of various tumors 13,14 including GBM, 15 where it has been proposed to participate in late phase angiogenesis. 16 Whereas early phase angiogenesis involves endothelial cell proliferation and migration, late phase angiogenesis is characterized by reconstitution of vascular basement membrane, establishment of cell-cell junctions and pericyte recruitment and integration into the vessel wall. 17,18 In addition to its suggested…”

Section: Introductionmentioning

confidence: 99%

Insulin-like growth factor binding protein 7 exhibits tumor suppressive and vessel stabilization properties in U87MG and T98G glioblastoma cell lines

Pen

Durocher²,

Slinn³

et al. 2011

Cancer Biology & Therapy

View full text Add to dashboard Cite

“…IGFBP7 is described to induce the formation of an extensive network of capillary-like tubes of human brain endothelial cells, consecutive to TGFβ administration. This upregulation of IGFBP7 by TGFβ requires ALK/SMAD2 pathway's activation (Pen et al, 2008). This in vitro finding suggests that TGFβ may utilize IGBP7 which is abundantly expressed in GBM vessels, to promote tumor vessels formation.…”

Section: Tgfβ Subfamily Promotes Angiogenesismentioning

confidence: 78%

Overview of Transforming Growth Factor β Superfamily Involvement in Glioblastoma Initiation and Progression

Nana¹,

Yang²,

Lin³

2015

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive of human brain tumors and has a stunning progression with a mean survival of one year from the date of diagnosis. High cell proliferation, angiogenesis and/or necrosis are histopathological features of this cancer, which has no efficient curative therapy. This aggressiveness is associated with particular heterogeneity of the tumor featuring multiple genetic and epigenetic alterations, but also with implications of aberrant signaling driven by growth factors. The transforming growth factor β (TGFβ) superfamily is a large group of structurally related proteins including TGFβ subfamily members Nodal, Activin, Lefty, bone morphogenetic proteins (BMPs) and growth and differentiation factor (GDF). It is involved in important biological functions including morphogenesis, embryonic development, adult stem cell differentiation, immune regulation, wound healing and inflammation. This superfamily is also considered to impact on cancer biology including that of GBM, with various effects depending on the member. The TGFβ subfamily, in particular, is overexpressed in some GBM types which exhibit aggressive phenotypes. This subfamily impairs anti-cancer immune responses in several ways, including immune cells inhibition and major histocompatibility (MHC) class I and II abolishment. It promotes GBM angiogenesis by inducing angiogenic factors such as vascular endothelial growth factor (VEGF), plasminogen activator inhibitor (PAI-I) and insulinlike growth factor-binding protein 7 (IGFBP7), contributes to GBM progression by inducing metalloproteinases (MMPs), "pro-neoplastic" integrins (αvβ3, α5β1) and GBM initiating cells (GICs) as well as inducing a GBMmesenchymal phenotype. Equally, Nodal promotes GICs, induces cancer metabolic switch and supports GBM cell proliferation, but is negatively regulated by Lefty. Activin promotes GBM cell proliferation while GDF yields immune-escape function. On the other hand, BMPs target GICS and induce differentiation and sensitivity to chemotherapy. This multifaceted involvement of this superfamily in GBM necessitates different strategies in anti-cancer therapy. While suppressing the TGFβ subfamily yields advantageous results, enhancing BMPs production is also beneficial.

show abstract

Glioblastoma-secreted factors induce IGFBP7 and angiogenesis by modulating Smad-2-dependent TGF-β signaling

Cited by 99 publications

References 65 publications

Insulin-like growth factor binding protein 7 and tissue inhibitor of metalloproteinases-2: differential expression and secretion in human kidney tubule cells

Insulin-like growth factor binding protein 7 and tissue inhibitor of metalloproteinases-2: differential expression and secretion in human kidney tubule cells

Insulin-like growth factor binding protein 7 exhibits tumor suppressive and vessel stabilization properties in U87MG and T98G glioblastoma cell lines

Overview of Transforming Growth Factor β Superfamily Involvement in Glioblastoma Initiation and Progression

Contact Info

Product

Resources

About