Inhibition of breast cancer growth and metastasis by a biomimetic peptide

Lee, Esak; Lee, Seung-Jae; Koskimaki, Jacob E.; Han, Zheyi; Pandey, Niranjan B.; Popel, Aleksander S.

doi:10.1038/srep07139

Cited by 41 publications

(54 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In agreement with these data, the peptide SP5031 significantly reduced VEGF-induced angiogenesis, which was measured by staining with CD34 in an in vivo subcutaneous Matrigel plug assay. Using a collagen-derived biomimetic peptide SP2043, a 95% reduction in migration would inhibit bifurcations and vascular segment density enough to inhibit angiogenesis so treating with 25 μM of SP2043 is predicted to be sufficient to inhibit angiogenesis in agreement with experimental data53.…”

Section: Discussionsupporting

confidence: 56%

Effects of endothelial cell proliferation and migration rates in a computational model of sprouting angiogenesis

Norton

Popel

2016

Sci Rep

Self Cite

120

View full text Add to dashboard Cite

Angiogenesis, the recruitment of new blood vessels, is a critical process for the growth, expansion, and metastatic dissemination of developing tumors. Three types of cells make up the new vasculature: tip cells, which migrate in response to gradients of vascular endothelial growth factor (VEGF), stalk cells, which proliferate and extend the vessels, and phalanx cells, which are quiescent and support the sprout. In this study we examine the contribution of tip cell migration rate and stalk cell proliferation rate on the formation of new vasculature. We calculate several vascular metrics, such as the number of vascular bifurcations per unit volume, vascular segment length per unit volume, and vascular tortuosity. These measurements predict that proliferation rate has a greater effect on the spread and extent of vascular growth compared to migration rate. Together, these findings provide strong implications for designing anti-angiogenic therapies that may differentially target endothelial cell proliferation and migration. Computational models can be used to predict optimal anti-angiogenic therapies in combination with other therapeutics to improve outcome.

show abstract

Section: Discussionsupporting

confidence: 56%

Effects of endothelial cell proliferation and migration rates in a computational model of sprouting angiogenesis

Norton

Popel

2016

Sci Rep

Self Cite

120

View full text Add to dashboard Cite

show abstract

“…The measurement of tube formation was determined as previously described (Lee et al, 2014) by ImageJ with the angiogenesis tool (US National Institutes of Health). Tube formation was examined under an inverted microscope and photographed at ×25 magnification 4 h after cell seeding.…”

Section: Tube Formationmentioning

confidence: 99%

Skeletal muscle‐derived exosomes regulate endothelial cell functions via reactive oxygen species‐activated nuclear factor‐κB signalling

Nie

Sato

Garner

et al. 2019

Experimental Physiology

View full text Add to dashboard Cite

New Findings What is the central question of this study?Capillary rarefaction is found in diabetic and aged muscle, whereas exercise increases skeletal muscle angiogenesis. The association implies a crosstalk between muscle cells and endothelial cells. The underlying mechanisms mediating the crosstalk between these cells remains to be elucidated fully. What is the main finding and its importance?Endothelial cell functions are regulated by skeletal muscle cell‐derived exosomes via a vascular endothelial growth factor‐independent pathway. This study reveals a new mechanism mediating the crosstalk between skeletal muscle cells and endothelial cells. Abstract Loss of skeletal muscle capillarization, known as capillary rarefaction, is found in type 2 diabetes, chronic heart failure and healthy ageing and is associated with impaired delivery of substrates to the muscle. However, the interaction and communication of skeletal muscle with endothelial cells in the regulation of capillaries surrounding the muscle remains elusive. Exosomes are a type of secreted extracellular vesicle containing mRNAs, proteins and, especially, microRNAs that exert paracrine and endocrine effects. In this study, we investigated whether skeletal muscle‐derived exosomes (SkM‐Exo) regulate the endothelial cell functions of angiogenesis. We demonstrated that C2C12 myotube‐derived exosomes improved endothelial cell functions, assessed by the proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs), which were increased by 20, 23 and 40%, respectively, after SkM‐Exo exposure. The SkM‐Exo failed to activate HUVEC vascular endothelial growth factor (VEGF) signalling. The SkM‐Exo increased HUVEC reactive oxygen species and activated the nuclear factor‐κB pathway, suggesting that SkM‐Exo‐induced angiogenesis was mediated by a VEGF‐independent pathway. In addition, several angiogenic microRNAs were packaged in SkM‐Exo, with miR‐130a being particularly enriched and successfully transferred from SkM‐Exo to HUVECs. Delivery of miRNAs into endothelial cells might explain the enhancement of reactive oxygen species production and angiogenesis by SkM‐Exo. The potential angiogenic effect of SkM‐Exo could provide an effective therapy for promoting skeletal muscle angiogenesis in diseases characterized by capillary rarefaction or inadequate angiogenesis.

show abstract

“…Specifically in breast cancer, tumour LV are the predominant routes of tumour dissemination. Thus current interest in the application of anti-angiogenic agents as cancer therapeutics has led to strategies combining inhibitors of angiogenesis and lymphangiogenesis with the goal of developing more effective anti-cancer therapies (Refs 62, 105, 149, 150). …”

Section: Clinical Implications and Applicationsmentioning

confidence: 99%

Crosstalk between cancer cells and blood endothelial and lymphatic endothelial cells in tumour and organ microenvironment

Lee

Pandey

Popel

2015

Expert Rev. Mol. Med.

Self Cite

View full text Add to dashboard Cite

Tumour and organ microenvironments are crucial for cancer progression and metastasis. Crosstalk between multiple non-malignant cell types in the microenvironments and cancer cells promotes tumour growth and metastasis. Blood and lymphatic endothelial cells (BEC and LEC) are two of the components in the microenvironments. Tumour blood vessels (BV), comprising BEC, serve as conduits for blood supply into the tumour, and are important for tumour growth as well as haematogenous tumour dissemination. Lymphatic vessels (LV), comprising LEC, which are relatively leaky compared with BV, are essential for lymphogenous tumour dissemination. In addition to describing the conventional roles of the BV and LV, we also discuss newly emerging roles of these endothelial cells: their crosstalk with cancer cells via molecules secreted by the BEC and LEC (also called angiocrine and lymphangiocrine factors). This review suggests that BEC and LEC in various microenvironments can be orchestrators of tumour progression and proposes new mechanism-based strategies to discover new therapies to supplement conventional anti-angiogenic and anti-lymphangiogenic therapies.

show abstract

Inhibition of breast cancer growth and metastasis by a biomimetic peptide

Cited by 41 publications

References 51 publications

Effects of endothelial cell proliferation and migration rates in a computational model of sprouting angiogenesis

Effects of endothelial cell proliferation and migration rates in a computational model of sprouting angiogenesis

Skeletal muscle‐derived exosomes regulate endothelial cell functions via reactive oxygen species‐activated nuclear factor‐κB signalling

Crosstalk between cancer cells and blood endothelial and lymphatic endothelial cells in tumour and organ microenvironment

Contact Info

Product

Resources

About