Bioengineered three-dimensional co-culture of cancer cells and endothelial cells: A model system for dual analysis of tumor growth and angiogenesis

2017 ◽  
Vol 114 (8) ◽  
pp. 1865-1877 ◽  
Author(s):  
Geraldine Giap Ying Chiew ◽  
Na Wei ◽  
Samiksha Sultania ◽  
Sierin Lim ◽  
Kathy Qian Luo
Keyword(s):  
Endothelial Cells ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Three Dimensional ◽  
Model System ◽  
Dual Analysis

scholarly journals The anti-angiogenic tyrosine kinase inhibitor Pazopanib kills cancer cells and disrupts endothelial networks in biomimetic three-dimensional renal tumouroids

2020 ◽  
Vol 11 ◽  
pp. 204173142092059
Author(s):  
Katerina Stamati ◽  
Patricia A Redondo ◽  
Agata Nyga ◽  
Joana B Neves ◽  
Maxine GB Tran ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Endothelial Cells ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Three Dimensional ◽  
Carcinoma Cells

Pazopanib is a tyrosine kinase inhibitor used to treat renal cell carcinoma. Few in vitro studies investigate its effects towards cancer cells or endothelial cells in the presence of cancer. We tested the effect of Pazopanib on renal cell carcinoma cells (CAKI-2,786-O) in two-dimensional and three-dimensional tumouroids made of dense extracellular matrix, treated in normoxia and hypoxia. Finally, we engineered complex tumouroids with a stromal compartment containing fibroblasts and endothelial cells. Simple CAKI-2 tumouroids were more resistant to Pazopanib than 786-O tumouroids. Under hypoxia, while the more ‘resistant’ CAKI-2 tumouroids showed no decrease in viability, 786-O tumouroids required higher Pazopanib concentrations to induce cell death. In complex tumouroids, Pazopanib exposure led to a reduction in the overall cell viability (p < 0.0001), disruption of endothelial networks and direct killing of renal cell carcinoma cells. We report a biomimetic multicellular tumouroid for drug testing, suitable for agents whose primary target is not confined to cancer cells.

Bi-directional interactions of prostate cancer cells and bone marrow endothelial cells in three-dimensional culture

The Prostate ◽  
2005 ◽  
Vol 64 (1) ◽  
pp. 75-82 ◽  
Author(s):  
Jeffrey M. Barrett ◽  
Kathy A. Mangold ◽  
Tamas Jilling ◽  
Karen L. Kaul
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Endothelial Cells ◽  
Cancer Cells ◽  
Three Dimensional ◽  
Prostate Cancer Cells ◽  
Three Dimensional Culture

scholarly journals HEYL Regulates Neoangiogenesis Through Overexpression in Both Breast Tumor Epithelium and Endothelium

2021 ◽  
Vol 10 ◽  
Author(s):  
Liangfeng Han ◽  
Preethi Korangath ◽  
Nguyen K. Nguyen ◽  
Adam Diehl ◽  
Soonweng Cho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Neutralizing Antibodies ◽  
Breast Cancer Cells ◽  
Vascular Endothelial Cells ◽  
Downstream Target ◽  
Mammary Tumor Cells

Blocking tumor angiogenesis is an appealing therapeutic strategy, but to date, success has been elusive. We previously identified HEYL, a downstream target of Notch signaling, as an overexpressed gene in both breast cancer cells and as a tumor endothelial marker, suggesting that HEYL overexpression in both compartments may contribute to neoangiogenesis. Carcinomas arising in double transgenic Her2-neu/HeyL mice showed higher tumor vessel density and significantly faster growth than tumors in parental Her2/neu mice. Providing mechanistic insight, microarray-based mRNA profiling of HS578T-tet-off-HEYL human breast cancer cells revealed upregulation of several angiogenic factors including CXCL1/2/3 upon HEYL expression, which was validated by RT-qPCR and protein array analysis. Upregulation of the cytokines CXCL1/2/3 occurred through direct binding of HEYL to their promoter sequences. We found that vessel growth and migration of human vascular endothelial cells (HUVECs) was promoted by conditioned medium from HS578T-tet-off-HEYL carcinoma cells, but was blocked by neutralizing antibodies against CXCL1/2/3. Supporting these findings, suppressing HEYL expression using shRNA in MDA-MB-231 cells significantly reduced tumor growth. In addition, suppressing the action of proangiogenic cytokines induced by HEYL using a small molecule inhibitor of the CXCl1/2/3 receptor, CXCR2, in combination with the anti-VEGF monoclonal antibody, bevacizumab, significantly reduced tumor growth of MDA-MB-231 xenografts. Thus, HEYL expression in tumor epithelium has a profound effect on the vascular microenvironment in promoting neoangiogenesis. Furthermore, we show that lack of HEYL expression in endothelial cells leads to defects in neoangiogenesis, both under normal physiological conditions and in cancer. Thus, HeyL-/- mice showed impaired vessel outgrowth in the neonatal retina, while the growth of mammary tumor cells E0771 was retarded in syngeneic HeyL-/- mice compared to wild type C57/Bl6 mice. Blocking HEYL’s angiogenesis-promoting function in both tumor cells and tumor-associated endothelium may enhance efficacy of therapy targeting the tumor vasculature in breast cancer.

scholarly journals Migration of endothelial cells into photo-responsive hydrogels with tunable modulus under the presence of pro-inflammatory macrophages

2019 ◽  
Vol 6 (5) ◽  
pp. 259-267 ◽  
Author(s):  
Wangbei Cao ◽  
Xuguang Li ◽  
Xingang Zuo ◽  
Changyou Gao
Keyword(s):  
Endothelial Cells ◽  
Uv Irradiation ◽  
Tissue Regeneration ◽  
Three Dimensional ◽  
Mesh Size ◽  
Model System ◽  
Biological Processes ◽  
M1 Macrophages ◽  
Inflammatory Macrophages ◽  
Responsive Hydrogels

Abstract Cell migration in three-dimensional environment is extremely important for tissue regeneration and other biological processes. In this work, a model system was developed to study how endothelial cells (ECs) migrate into photo-responsive hydrogels under the presence of pro-inflammatory macrophages. The hydrogel was synthesized from hyaluronic acid grafted with coumarin and methacrylate moieties by both carbon–carbon covalent linking and coumarin dimerization under UV irradiation at 365 nm. The structure of the hydrogel was conveniently modulated by UV irradiation at 254 nm to decompose the coumarin dimers, leading to the significant decrease of modulus and increase of swelling ratio and mesh size. Under the presence of M1 macrophages, ECs were induced to migrate into the hydrogels with a different degree. A significant larger net displacement of ECs was found in the softer hydrogel obtained by irradiation with UV at 254 nm than in the stiffer original one at day 7.

A three-dimensional model system to study the interactions between human leukocytes and endothelial cells

1990 ◽  
Vol 20 (12) ◽  
pp. 2775-2781 ◽  
Author(s):  
Betty C. Hakkert ◽  
Jeannette M. Rentenaar ◽  
Willem G. Van Aken ◽  
Dirk Roos ◽  
Jan A. Van Mourik
Keyword(s):  
Endothelial Cells ◽  
Three Dimensional ◽  
Model System ◽  
Dimensional Model ◽  
Three Dimensional Model ◽  
Human Leukocytes

Effect of Synthetic Peptides Derived from Human Apo(a) on Cell Proliferation, VEGF Production, and Angiogenesis in Cancer Cells and Vascular Endothelial Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3904-3904 ◽  
Author(s):  
Bin Bao ◽  
Ananda S. Prasad ◽  
Dex Dou ◽  
Steve Jin ◽  
Ginny W. Bao
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Synthetic Peptides ◽  
Vascular Endothelial Cells ◽  
The Body ◽  
Vascular Endothelial ◽  
Angiogenic Activity ◽  
Peptide Treatment

Abstract Angiogenesis, the formation of new blood vessels from the existing vascular bed, has been described as one of the hallmarks of cancer, and plays an essential role in tumor growth, invasion, and metastasis. The development of specific anti-angiogenic agents is an attractive therapeutic approach for the treatment of cancer. Apolipoprotein, Apo(a), is a large glycoprotein with multiple kringle structures, which play an important role in regulating the intermolecular reaction in the body. The evidence shows that Apo(a) has anti-angiogenic activity on vascular endothelial cells and inhibits tumor growth in mice. The 38th kringle on Apo(a) has been found to be homologous to the kringle 5 of plasminogen, a known endogenous anti-angiogenic kringle structure. According to our preliminary study, the 38th kringle of Apo(a) had an inhibitory effect on bovine capillary endothelial (BCE) cells. Seven peptides of the 38th kringle on Apo(a) were synthesized for screening of anti-angiogenic activity. Two synthetic peptides (P4 and P5) based on the 38th kringle structure sequence of Apo(a) were found to inhibit the proliferation of BCE cells. In the current study, we examined the effects of P4 and P5 synthetic peptides on cell proliferation by MTT assay, and VEGF production by ELIAS assay in human prostate cancer cells (C4-2B, LNCap, and PC3), and/or vascular endothelial cells such as human aortic endothelial cells (HAEC), human umbilical vein endothelial cell (HUVEC), and mouse microvascular endothelial cells (MVEC) after 2 days of incubation. The results are shown in the Table 1 and 2 below. Table 1. Effect of synthetic peptides on cell proliferation in cancer and vascular endothelial cells (%) P4 P5 Cell proliferation assay was conducted by MTT methos. The % of cell proliferation in peptide treatment groups was compared to the cells without peptide treatment HAEC 64.7±16.4 62.4±12.0 HUVEC 59.4±3.7 71.7±1.2 MVEC 76.9±6.1 75.8±5.6 C4-2B 64.1±5.1 60.9±4.3 LNCap 77.9±2.9 51.8±1.6 PC3 75.8±3.4 75.4±3.6 Table 2. Effect of synthetic peptides on VEGF production in cancer cells (pg/mL) Control P4 P5 C4-2B 905.0±87.7 694.1±99.1 720.1±106.2 LNCap 1116.5±191.6 717.9±100.1 794.3±119.7 PC3 902.6±52.0 743.2±123.7 721.3±92.7 Our data indicate that these synthetic peptides inhibited the cell proliferation and VEGF production. We also examined the effect of P4 and P5 peptides on angiogenesis in HAEC and MVEC cells after 10h of incubation by Matrigel tube formation assay. The data indicate that angiogenesis declined by 40–50% when P4 or P5 was added to the cell culture. All these data suggest that P4 and P5, synthetic peptides derived from the 38th Kringle of Apo(a) have anti-proliferative and anti-angiogenic effects, which may potentially be applicable for cancer treatment. Further studies are in progress in order to define the mechanisms action of these peptides.

scholarly journals Effect of differences in cancer cells and tumor growth sites on recruiting bone marrow-derived endothelial cells and myofibroblasts in cancer-induced stroma

2005 ◽  
Vol 115 (6) ◽  
pp. 885-892 ◽  
Author(s):  
Takafumi Sangai ◽  
Genichiro Ishii ◽  
Keiji Kodama ◽  
Shin'ichi Miyamoto ◽  
Yasuyuki Aoyagi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Tumor Growth ◽  
Cancer Cells
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