Matrilin-1 Is an Inhibitor of Neovascularization

Foradori, Matthew J.; Chen, Qian; Fernández, Cecilia A.; Harper, Jay; Li, Xin; Tsang, Patricia; Langer, Robert; Moses, Marsha A.

doi:10.1074/jbc.m113.529982

Cited by 18 publications

(18 citation statements)

References 48 publications

(60 reference statements)

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“…Other authors indirectly observed the basic role of anti‐angiogenic factors involved in development, for example Foradori et al . observed that, in Matrilin‐1‐deficient mice, the angiogenesis during fracture healing was significantly higher in Matrilin‐1−/− mice compared to the wild‐type mice, as demonstrated by elevated expression of angiogenesis markers including PECAM1, VEGFR and VE‐cadherin in that cartilage. When we consider the results of the present study, as a whole, we can observe a clear switch between the expression of SOX9 and COLL II, while the peak level of ENDO corresponded to the intermediate young age.…”

Section: Discussionmentioning

confidence: 95%

Age‐related modulation of angiogenesis‐regulating factors in the swine meniscus

Giancamillo

Deponti

Modina

et al. 2017

J Cellular Molecular Medi

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An in‐depth knowledge of the native meniscus morphology and biomechanics in its different areas is essential to develop an engineered tissue. Meniscus is characterized by a great regional variation in extracellular matrix components and in vascularization. Then, the aim of this work was to characterize the expression of factors involved in angiogenesis in different areas during meniscus maturation in pigs. The menisci were removed from the knee joints of neonatal, young and adult pigs, and they were divided into the inner, intermediate and outer areas. Vascular characterization and meniscal maturation were evaluated by immunohistochemistry and Western blot analysis. In particular, expression of the angiogenic factor Vascular Endothelial Growth Factor (VEGF) and the anti‐angiogenic marker Endostatin (ENDO) was analysed, as well as the vascular endothelial cadherin (Ve‐CAD). In addition, expression of Collagen II (COLL II) and SOX9 was examined, as markers of the fibro‐cartilaginous differentiation. Expression of VEGF and Ve‐CAD had a similar pattern in all animals, with a significant increase from the inner to the outer part of the meniscus. Pooling the zones, expression of both proteins was significantly higher in the neonatal meniscus than in young and adult menisci. Conversely, the young meniscus revealed a significantly higher expression of ENDO compared to the neonatal and adult ones. Analysis of tissue maturation markers showed an increase in COLL II and a decrease in SOX9 expression with age. These preliminary data highlight some of the changes that occur in the swine meniscus during growth, in particular the ensemble of regulatory factors involved in angiogenesis.

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Section: Discussionmentioning

confidence: 95%

Age‐related modulation of angiogenesis‐regulating factors in the swine meniscus

Giancamillo

Deponti

Modina

et al. 2017

J Cellular Molecular Medi

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“…We next determined the anti-angiogenic impact of ICAM-Lcn2-LPs using three in vitro angiogenic assays: human endothelial cell proliferation, migration, and tube formation. 23 , 24 , 26 Human microvascular endothelial cells (HMVECs) and human umbilical vein endothelial cells (HUVECs) were chosen as two representative normal human endothelial cell lines. We first examined the effect of ICAM-Lcn2-LP treatment on endothelial cell proliferation.…”

Section: Resultsmentioning

confidence: 99%

“…Endothelial cell proliferation was measured using our previously reported protocol with modifications. 23 , 24 5 × 10 3 human endothelial cells (HMVECs or HUVECs) were plated in each well of a 96-well plate and treated for 48 h with CM harvested from MDA-MB-231 treated with (1) PBS (control), (2) Free Lcn2 siRNA, (3) ICAM-SCR-LP, (4) Lcn2-LIPO, (5) IgG-Lcn2-LP, and (6) ICAM-Lcn2-LP at the final siRNA concentration of 100 nM as described above. The human endothelial cell proliferation was analyzed using a Dojindo cell counting kit using the protocol from the Dojindo Molecular Technologies (Rockville, MD, USA).…”

Section: Methodsmentioning

confidence: 99%

“…The CAM assay was performed as previously reported by us. 24 - 28 Fertilized chicken embryos (Charles River Laboratories, North Franklin, CT) were cultured in-ova . At developmental day 7, 5 μL of serum-free media (1) (negative control) or CMs harvested from MDA-MB-231 cells treated with the following agents: (2) PBS (sham), (3) IgG-Lcn2-LP, and (4) ICAM-Lcn2-LP at the final siRNA concentration of 100 nM as described above, was applied to a piece of filter paper-based substrate (2 mm in diameter) on the CAM.…”

Section: Methodsmentioning

confidence: 99%

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ICAM-1-Targeted, Lcn2 siRNA-Encapsulating Liposomes are Potent Anti-angiogenic Agents for Triple Negative Breast Cancer

et al. 2016

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Lipocalin 2 (Lcn2) is a promising therapeutic target as well as a potential diagnostic biomarker for breast cancer. It has been previously shown to promote breast cancer progression by inducing the epithelial to mesenchymal transition in breast cancer cells as well as by enhancing angiogenesis. Lcn2 levels in urine and tissue samples of breast cancer patients has also been correlated with breast cancer status and poor patient prognosis. In this study, we have engineered a novel liposomal small interfering RNA (siRNA) delivery system to target triple negative breast cancer (TNBC) via a recently identified molecular target, intercellular adhesion molecule-1 (ICAM-1). This ICAM-1-targeted, Lcn2 siRNA- encapsulating liposome (ICAM-Lcn2-LP) binds human TNBC MDA-MB-231cells significantly stronger than non-neoplastic MCF-10A cells. Efficient Lcn2 knockdown by ICAM-Lcn2-LPs led to a significant reduction in the production of vascular endothelial growth factor (VEGF) from MDA-MB-231 cells, which, in turn, led to reduced angiogenesis both in vitro and in vivo. Angiogenesis (neovascularization) is a requirement for solid tumor growth and progression, and its inhibition is an important therapeutic strategy for human cancers. Our results indicate that a tumor-specific strategy such as the TNBC-targeted, anti-angiogenic therapeutic approach developed here, may be clinically useful in inhibiting TNBC progression.

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“…Proliferation assays were performed as previously described by us (16,(20)(21)(22). In brief, HMVEC-D, HMVEC-L, and HMVEC-M cells transfected with control siRNA or siZNF24 were serum starved overnight and seeded in EGM-2 MV at 5000 cells per well in triplicate in 48-well plates.…”

Section: Proliferation and Apoptosis Assaysmentioning

confidence: 99%

The endogenous zinc finger transcription factor, ZNF24, modulates the angiogenic potential of human microvascular endothelial cells

et al. 2014

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We have previously identified a zinc finger transcription factor, ZNF24 (zinc finger protein 24), as a novel inhibitor of tumor angiogenesis and have demonstrated that ZNF24 exerts this effect by repressing the transcription of VEGF in breast cancer cells. Here we focused on the role of ZNF24 in modulating the angiogenic potential of the endothelial compartment. Knockdown of ZNF24 by siRNA in human primary microvascular endothelial cells (ECs) led to significantly decreased cell migration and invasion compared with control siRNA. ZNF24 knockdown consistently led to significantly impaired VEGF receptor 2 (VEGFR2) signaling and decreased levels of matrix metalloproteinase-2 (MMP-2), with no effect on levels of major regulators of MMP-2 activity such as the tissue inhibitors of metalloproteinases and MMP-14. Moreover, silencing ZNF24 in these cells led to significantly decreased EC proliferation. Quantitative PCR array analyses identified multiple cell cycle regulators as potential ZNF24 downstream targets which may be responsible for the decreased proliferation in ECs. In vivo, knockdown of ZNF24 specifically in microvascular ECs led to significantly decreased formation of functional vascular networks. Taken together, these results demonstrate that ZNF24 plays an essential role in modulating the angiogenic potential of microvascular ECs by regulating the proliferation, migration, and invasion of these cells.-Jia, D., Huang, L., Bischoff, J., Moses, M. A. The endogenous zinc finger transcription factor, ZNF24, modulates the angiogenic potential of human microvascular endothelial cells. FASEB J. 29, 1371-1382 (2015). www.fasebj.org

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Matrilin-1 Is an Inhibitor of Neovascularization

Cited by 18 publications

References 48 publications

Age‐related modulation of angiogenesis‐regulating factors in the swine meniscus

Age‐related modulation of angiogenesis‐regulating factors in the swine meniscus

ICAM-1-Targeted, Lcn2 siRNA-Encapsulating Liposomes are Potent Anti-angiogenic Agents for Triple Negative Breast Cancer

The endogenous zinc finger transcription factor, ZNF24, modulates the angiogenic potential of human microvascular endothelial cells

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