Vascular zip codes in angiogenesis and metastasis

2004 ◽  
Vol 32 (3) ◽  
pp. 397-402 ◽  
Author(s):  
E. Ruoslahti
Keyword(s):  
Blood Vessels ◽  
Lymphatic Vessels ◽  
Therapeutic Agents ◽  
In Vivo Screening ◽  
Normal Tissues ◽  
Tumour Metastasis ◽  
Selective Expression ◽  
Vascular Markers ◽  
Tumour Blood

In vivo screening of phage-displayed peptide libraries has revealed extensive molecular differences in the blood vessels of individual normal tissues. Pathological lesions also put their signature on the vasculature; in tumours, both blood and lymphatic vessels differ from normal vessels. The changes that characterize tumour blood vessels include selective expression of certain integrins. Peptides isolated by in vivo phage display for homing to tumours have been shown to be useful in directing therapeutic agents to experimental tumours. The targeting can enhance the efficacy of the therapy while reducing side effects. Phage screening has also revealed lung-specific vascular markers that promote tumour metastasis to the lungs by mediating specific adherence of tumour cells to the lung vasculature. These phage-screening studies have revealed a previously unsuspected degree of vascular specialization and provide potentially useful guidance devices for targeted therapies.

scholarly journals circLMTK2 acts as a sponge of miR-150-5p and promotes proliferation and metastasis in gastric cancer

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Sen Wang ◽  
Dong Tang ◽  
Wei Wang ◽  
Yining Yang ◽  
Xiaoqing Wu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Bioinformatic Analysis ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Normal Tissues ◽  
Tumour Metastasis ◽  
Genome Wide ◽  
Proliferation And Metastasis

Abstract Background As a novel class of non-coding RNAs, circular RNAs (circRNAs) are key regulators of the development and progression of different cancers. However, little is known about the function and biological mechanism of circLMTK2, also named hsa_circ_0001725, in gastric cancer (GC) tumourigenesis. Methods circLMTK2 was identified in ten paired cancer specimens and adjacent normal tissues by RNA sequencing and genome-wide bioinformatic analysis and verified by quantitative real-time PCR (qRT-PCR). Knockdown or exogenous expression of circLMTK2 combined with in vitro and in vivo assays were performed to prove the functional significance of circLMTK2. The molecular mechanism of circLMTK2 was demonstrated by searching the CircNet database and confirmed by RNA in vivo precipitation assays, western blotting, luciferase assays and rescue experiments. Results circLMTK2 was frequently upregulated in GC tissues, and high circLMTK2 expression was associated with poor prognosis, lymph node metastasis and poor TNM stage in GC patients. Functionally, circLMTK2 overexpression promoted GC cell proliferation and tumourigenicity in vitro and in vivo. Furthermore, ectopic circLMTK2 expression enhanced GC cell migration and invasion in vitro and tumour metastasis in vivo. In addition, we demonstrated that circLMTK2 could sponge miR-150-5p, thus indirectly regulating the c-Myc expression and contributing to GC tumourigenesis. Conclusion Our findings demonstrate that circLMTK2 functions as a tumour promoter in GC through the miR-150-5p/c-Myc axis and could thus be a prognostic predictor and therapeutic target for GC.

scholarly journals Circular RNA _0008278 acts as a sponge of miR-378 and promotes proliferation and metastasis in gastric cancer

2021 ◽  
Author(s):  
Xuan Li ◽  
Haisheng Qian ◽  
Hao Dong ◽  
Yini Dang ◽  
Lei Peng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Bioinformatic Analysis ◽  
Potential Method ◽  
Circular Rna ◽  
Migration And Invasion ◽  
Normal Tissues ◽  
Tumour Metastasis ◽  
Regulatory Molecule

Abstract Background: Circular RNA (circRNA) is rising as an indispensable regulatory molecule in the progression of various kinds of malignant growth. However, little is known about the capacity and instruments of circRNA_0008727 in gastric cancer (GC). Our point was to recognize a novel circRNA-microRNA-mRNA useful system in gastric cancer. Method: CircRNA_0008278 was identified in three paired cancer specimens and adjacent normal tissues by RNA sequencing and genome-wide bioinformatic analysis and verified by quantitative real-time PCR (qRT-PCR). Knockdown or exogenous expression of circRNA_0008278 combined with in vitro and in vivo assays were performed to prove the functional significance of circRNA_0008278. The molecular mechanism of circRNA_0008278 was demonstrated by searching the CircNet database and confirmed by RNA in vivo precipitation assays, western blotting, luciferase assays and rescue experiments.Results: CircRNA_0008278 was frequently upregulated in GC tissues, and high circRNA_0008278 expression was associated with poor prognosis, lymph node metastasis and poor TNM stage in GC patients. Functionally, circRNA_0008278 overexpression promoted GC cell proliferation and tumourigenicity in vitro and in vivo. Furthermore, circRNA_0008278 over-expression enhanced GC cell migration and invasion in vitro and tumour metastasis in vivo. In addition, we demonstrated that circRNA_0008278 could sponge miR-378, thus indirectly regulating theYY1 expression and contributing to GC tumourigenesis.Conclusion: Our findings demonstrate that circRNA_0008278 functions as a tumour promoter in GC, and a new pathway circRNA_0008278/miR-378/YY1 which may be potential method for gastric cancer treatment.

In vivo dynamic light scattering microscopy of tumour blood vessels

2007 ◽  
Vol 228 (2) ◽  
pp. 118-122 ◽  
Author(s):  
V. KALCHENKO ◽  
D. PREISE ◽  
M. BAYEWITCH ◽  
I. FINE ◽  
K. BURD ◽  
...  
Keyword(s):  
Light Scattering ◽  
Dynamic Light Scattering ◽  
Blood Vessels ◽  
Tumour Blood

scholarly journals VEGFR3 does not sustain retinal angiogenesis without VEGFR2

2015 ◽  
Vol 112 (3) ◽  
pp. 761-766 ◽  
Author(s):  
Georgia Zarkada ◽  
Krista Heinolainen ◽  
Taija Makinen ◽  
Yoshiaki Kubota ◽  
Kari Alitalo
Keyword(s):  
Blood Vessels ◽  
Vascular System ◽  
Notch Pathway ◽  
Lymphatic Vessels ◽  
Signal Transduction Pathway ◽  
Retinal Angiogenesis ◽  
Vegfr2 Signaling ◽  
Endothelial Growth Factors ◽  
Tip Cells

Angiogenesis, the formation of new blood vessels, is regulated by vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs). VEGFR2 is abundant in the tip cells of angiogenic sprouts, where VEGF/VEGFR2 functions upstream of the delta-like ligand 4 (DLL4)/Notch signal transduction pathway. VEGFR3 is expressed in all endothelia and is indispensable for angiogenesis during early embryonic development. In adults, VEGFR3 is expressed in angiogenic blood vessels and some fenestrated endothelia. VEGFR3 is abundant in endothelial tip cells, where it activates Notch signaling, facilitating the conversion of tip cells to stalk cells during the stabilization of vascular branches. Subsequently, Notch activation suppresses VEGFR3 expression in a negative feedback loop. Here we used conditional deletions and a Notch pathway inhibitor to investigate the cross-talk between VEGFR2, VEGFR3, and Notch in vivo. We show that postnatal angiogenesis requires VEGFR2 signaling also in the absence of Notch or VEGFR3, and that even small amounts of VEGFR2 are able to sustain angiogenesis to some extent. We found that VEGFR2 is required independently of VEGFR3 for endothelial DLL4 up-regulation and angiogenic sprouting, and for VEGFR3 functions in angiogenesis. In contrast, VEGFR2 deletion had no effect, whereas VEGFR3 was essential for postnatal lymphangiogenesis, and even for lymphatic vessel maintenance in adult skin. Knowledge of these interactions and the signaling functions of VEGFRs in blood vessels and lymphatic vessels is essential for the therapeutic manipulation of the vascular system, especially when considering multitargeted antiangiogenic treatments.

scholarly journals Immunohistochemical Staining for Lymphatic and Blood Vessels in Normal Tissues: Comparison between Routinely Paraffin-Embedded Tissues and Frozen Sections

2021 ◽  
Vol 50 (1) ◽  
pp. 13
Author(s):  
Tatsuo Tomita
Keyword(s):  
Blood Vessels ◽  
Lymphatic Vessels ◽  
Immunocytochemical Staining ◽  
Frozen Sections ◽  
Normal Tissues ◽  
New Findings ◽  
Frozen Tissue ◽  
Cyclic Changes ◽  
And Function ◽  
Vessel Tree

<p><strong>Objective</strong>. In the current study, we compared the distribution of blood and lymphatic vessels from paraffin-embedded tissues with those of frozen tissues of normal human and rhesus monkey.</p><p><strong> Materials and Methods</strong>. We performed immunocytochemical staining for lymphatic and blood vessels using LYVE-1 for lymphatic vessels and von Willebrand factor (F-8) for blood ves- sels.</p><p><strong>Results</strong>. Normal tissues included spleen, lymph node, liver, pancreas, salivary gland, colon, diaphragm, heart, lung, thyroid, adrenal gland, kidney, ovary, endometrium, and prostate. Splenic sinusoids were stained for LYVE-1 and F-8 in the frozen sections, supporting that the sinusoid is a lymphoreticular system and blood vessel in structure and function. In frozen sections, the lymphatic sinusoids were consistently positive for LYVE-1, while hepatic sinusoids were positive for LYVE-1, but not for F-8. Thus, lymphatic and blood vessels were more readily detected in frozen tissue sections than in the paraffin-embedded sections. In the endometrium, lymphatic vessels were not diffusely immunostained in paraffin-embedded sections. However, frozen sections detected cyclic changes of lymphatic vessels, growing from basalis to functionalis in the menstrual cycle. Lymphatic vessels were immunostained in many organs using frozen sections. Small pulmonary blood vessels were not immunostained by F-8 in the periphery of the bronchial vessel tree most likely these smallest blood vessels were not immunostained due to less F-8 attached to their endothelia. Conclusion. The present findings illustrate the differences in the immunostaining of blood vessels in sections obtained from paraffin-embedded tissues and those from frozen tissue. These new findings may be relevant for the basic histology and histopathology of lymphatic and blood vessels.</p>

scholarly journals Elafin promotes tumour metastasis and attenuates the anti-metastatic effects of erlotinib via binding to EGFR in hepatocellular carcinoma

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Chenwei Wang ◽  
Yadi Liao ◽  
Wei He ◽  
Hong Zhang ◽  
Dinglan Zuo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Early Stage ◽  
Tissue Microarrays ◽  
Luciferase Reporter ◽  
Normal Tissues ◽  
Tumour Metastasis ◽  
Hcc Cells

Abstract Background Elafin is a serine protease inhibitor critical for host defence. We previously reported that Elafin was associated with the recurrence of early-stage hepatocellular carcinoma (HCC) after surgery. However, the exact role of Elafin in HCC remains obscure. Methods HCC tissue microarrays were used to investigate the correlation between Elafin expression and the prognosis of HCC patients. In vitro migration, invasion and wound healing assays and in vivo lung metastasis models were used to determine the role of Elafin in HCC metastasis. Mass spectrometry, co-immunoprecipitation, western blotting, and immunofluorescence staining assays were performed to uncover the mechanism of Elafin in HCC. Dual-luciferase reporter and chromatin immunoprecipitation assays were employed to observe the transcriptional regulation of Elafin. Results Elafin expression was frequently increased in HCC tissues compared to normal tissues, and high Elafin expression in HCC tissues was correlated with aggressive tumour phenotypes and a poor prognosis in HCC patients. Elafin dramatically enhanced the metastasis of HCC cells both in vitro and in vivo by interacting with EGFR and activating EGFR/AKT signalling. Moreover, Elafin attenuated the suppressive effects of erlotinib on HCC metastasis. Besides, Elafin was transcriptionally regulated by Sp1 in HCC cells. Clinically, Elafin expression was positively correlated with Sp1, Vimentin, and EGFR signalling in both our HCC tissue microarrays and TCGA database analysis. Conclusions Upregulation of Elafin by Sp1 enhanced HCC metastasis via EGFR/AKT pathway, and overexpression of Elafin attenuated the anti-metastatic effects of erlotinib, suggesting a valuable prognostic biomarker and therapeutic target for HCC.

scholarly journals Investigating lymphangiogenesis in vitro and in vivo using engineered human lymphatic vessel networks

2021 ◽  
Vol 118 (31) ◽  
pp. e2101931118
Author(s):  
Shira Landau ◽  
Abigail Newman ◽  
Shlomit Edri ◽  
Inbal Michael ◽  
Shahar Ben-Shaul ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Vessel ◽  
Blood Vessels ◽  
Lymphatic Vessel ◽  
Lymphatic Vessels ◽  
Lymphatic Endothelial Cells ◽  
Supporting Cells ◽  
Vessel Formation ◽  
Vessel Networks

The lymphatic system is involved in various biological processes, including fluid transport from the interstitium into the venous circulation, lipid absorption, and immune cell trafficking. Despite its critical role in homeostasis, lymphangiogenesis (lymphatic vessel formation) is less widely studied than its counterpart, angiogenesis (blood vessel formation). Although the incorporation of lymphatic vasculature in engineered tissues or organoids would enable more precise mimicry of native tissue, few studies have focused on creating engineered tissues containing lymphatic vessels. Here, we populated thick collagen sheets with human lymphatic endothelial cells, combined with supporting cells and blood endothelial cells, and examined lymphangiogenesis within the resulting constructs. Our model required just a few days to develop a functional lymphatic vessel network, in contrast to other reported models requiring several weeks. Coculture of lymphatic endothelial cells with the appropriate supporting cells and intact PDGFR-β signaling proved essential for the lymphangiogenesis process. Additionally, subjecting the constructs to cyclic stretch enabled the creation of complex muscle tissue aligned with the lymphatic and blood vessel networks, more precisely biomimicking native tissue. Interestingly, the response of developing lymphatic vessels to tensile forces was different from that of blood vessels; while blood vessels oriented perpendicularly to the stretch direction, lymphatic vessels mostly oriented in parallel to the stretch direction. Implantation of the engineered lymphatic constructs into a mouse abdominal wall muscle resulted in anastomosis between host and implant lymphatic vasculatures, demonstrating the engineered construct's potential functionality in vivo. Overall, this model provides a potential platform for investigating lymphangiogenesis and lymphatic disease mechanisms.

scholarly journals A novel pro-lymphangiogenic function for Th17/IL-17

Blood ◽  
2011 ◽  
Vol 118 (17) ◽  
pp. 4630-4634 ◽  
Author(s):  
Sunil K. Chauhan ◽  
Yiping Jin ◽  
Sunali Goyal ◽  
Hyun Soo Lee ◽  
Thomas A. Fuchsluger ◽  
...  
Keyword(s):  
Cell Culture ◽  
Endothelial Cells ◽  
Autoimmune Diseases ◽  
Blood Vessels ◽  
Th17 Cells ◽  
Lymphatic Vessels ◽  
Preclinical Model ◽  
Lymphatic Endothelial Cells ◽  
Corneal Lymphangiogenesis

Abstract Th17 cells, in addition to their proinflammatory functions, have been recognized as potent inducers of angiogenesis in autoimmune diseases and malignancies. In the present study, we demonstrate distinct mechanisms by which IL-17 induces lymphangiogenesis. Using the mouse cornea micropocket and cell culture assays, our data demonstrate that IL-17 directly promotes growth of lymphatic vessels by inducing increased expression of prolymphangiogenic VEGF-D and proliferation of lymphatic endothelial cells. However, IL-17–induced growth of blood vessels is primarily mediated through IL-1β secretion by IL-17–responsive cells. Furthermore, in vivo blockade of IL-17 in a preclinical model of Th17-dominant autoimmune ocular disease demonstrates a significant reduction in the corneal lymphangiogenesis and in the progression of clinical disease. Taken together, our findings demonstrate a novel prolymphangiogenic function for Th17/IL-17, indicating that IL-17 can promote the progression and amplification of immunity in part through its induction of lymphangiogenesis.

scholarly journals Low efficiency of leucocyte plugging-based drug delivery to cancer in mice

2021 ◽  
Author(s):  
Baifeng Qian ◽  
Andreas Termer ◽  
Christof M. Sommer ◽  
Arianeb Mehrabi ◽  
Eduard Ryschich
Keyword(s):  
Drug Delivery ◽  
Blood Vessels ◽  
Ex Vivo ◽  
Human Neutrophils ◽  
Specific Cell ◽  
Specific Drug ◽  
Site Specific ◽  
Tumour Blood

AbstractCells of the immune system were proposed for use as Trojan horse for tumour-specific drug delivery. The efficacy of such cell-based drug delivery depends on the site-specific cell homing. This present study was aimed to investigate the potential of leucocytes for intratumoural site-specific enrichment using a locoregional application route in experimental liver tumours. Human neutrophils were isolated from peripheral blood and directly labelled with calcein AM or loaded with doxorubicin. The neutrophil loading and release of doxorubicin and the migration and adhesion to ICAM-1 were analysed in vitro. Macrophages were isolated and activated in vitro. Leucocyte plugging and the distribution pattern in the liver microvasculature were studied ex vivo, and the efficacy of leucocyte plugging in tumour blood vessels was analysed in vivo after superselective intra-arterial injection in mouse liver tumour models. Neutrophils were characterised by the high dose-dependent uptake and rapid release of doxorubicin. Doxorubicin loading did not affect neutrophil migration function. Neutrophil plugging in liver microvasculature was very high (> 90%), both after ex vivo perfusion and after injection in vivo. However, neutrophils as well as activated macrophages plugged insufficiently in tumour blood vessels and passed through the tumour microvasculture with a very low sequestration rate in vivo. Neutrophils possess several properties to function as potentially effective drug carriers; however, the tumour site-specific drug delivery after selective locoregional injection was observed to be insufficient owing to low intratumoural microvascular plugging. Graphical abstract

Clinical Evaluation of Radio-Labelled Bleomycin for Tumor Detection

1978 ◽  
Vol 17 (06) ◽  
pp. 238-248
Author(s):  
H. Beekhuis ◽  
M.A.P.C. van de Poll ◽  
A. Versluis ◽  
H. Jurjens ◽  
M.G. Woldring ◽  
...  
Keyword(s):  
Clinical Evaluation ◽  
Acidic Solution ◽  
Tumor Detection ◽  
Neutral Solution ◽  
Normal Tissues ◽  
Patients With Cancer ◽  
Tumor Bearing

Investigations with bleomycin labelled with radionuclides other than 57Co in patients with cancer and in tumor-bearing animals are described. In patients 57Co-bleo appears to be a better tumor-seeking radiopharmaceutical than 111In-bleo, 99mTc-bleo or 197Hg-bleo. This can be explained by a higher stability in vivo and a better tumor-seeking property of 57Co-bleo and less disturbing activity in the cardiac pool and in bone and other normal tissues when assessing the scintigram.Results with 111In-bleo labelled in acidic solution are not essentially different from those with 111In-bleo labelled in neutral solution.Results of 197Hg-bleo are almost identical with those of 197HgCl2 regarding the tumor-seeking effect as well as the distribution in normal tissues and organs. Probably the complex of 197Hg to bleomycin is not stable in vivo. The superiority of 57Co-bleo over 99mTc-bleo, 197Hg-bleo and also over 67Cu-bleo is confirmed by experiments on tumor bearing animals.We may conclude that the indication for use of bleomycin as a tumor-seeking pharmaceutical labelled with 111In, 99mTc, 197Hg or 67Cu seems to be very limited.

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