Abstract:
:Lymphangiogenesis is thought to be essential for cancer progression, making it an important target in cancer therapy. Lymphangiogenic factors (VEGF-C and VEGF-D) are upregulated in various tumors/cancers, and play an important role in lymphangiogenesis and lymph node metastasis. Similarly, semaphorin 4D (Sema4D) is a potent inducer of angiogenesis, and its overexpression is associated with tumor progression and poor prognosis in a variety of malignancies. However, little is known regarding the functional relationship between Sema4D and VEGF-C/VEGF-D and in the mediation of lymphangiogenesis and lymph node metastasis and clinical outcome. The current study aimed to evaluate the effect of Sema4D expression on outcome in patients with cervical cancer, and to explore the molecular mechanism of Sema4D in tumor progression. We evaluated Sema4D expression, density of lymphatic vessels, and invasion of lymphatic vessels with immunohistochemical methods in 232 human cervical cancers with long-term follow-up. Sema4D expression was correlated with patho-clinical parameters and patients' outcome. A cervical cancer cell line was used to investigate the contribution of sema4D to tumor progression by studying the role of Sema4D in VEGF-C/-D and cell migration using reverse transcription-polymerase chain reaction and Western blotting. We observed that Sema4D expression was higher in metastatic cervical cancer than in nonmetastatic cervical cancer (P<0.001). CD34-positive or D2-40-positive lymphatic vessel density was significantly increased in cases with lymph node metastasis compared with those without lymph node metastasis. The increased Sema4D expression was associated with VEGF-C/-D, the presence of lymphatic invasion, the occurrence of lymph node metastasis, and FIGO stage. We also observed a novel association between Sema4D upregulation and poor prognosis in cervical cancer. In vitro, the Sema4D inhibitory antibody and Sema4D-shRNA suppressed VEGF-C and VEGF-D in the human cervical carcinoma cell lines HeLa, Siha, and Caski cells. Invasiveness assay demonstrated that Sema4D could augment the invasive potential of the tumor cells in the cervical cancer lines and induction of cellular invasiveness by Sema4D stimulation could be inhibited by knockdown of plexinB1 by siRNA. Further mechanistic investigations of tumor cell invasiveness showed that Sema4D could induce activation of GTPase Ras homolog gene family, member A (RhoA), MAPK and AKT. In addition, plexinB1 knockdown by siRNA could suppress the Sema4D signal transmitted to MAPK and Akt. Taken together, these results suggest that Sema4D autocrine within tumor cells contributes to enhanced invasion and tumor progression through increased motility of cervical cancer and VEGF-C/-D-mediated lymphangiogenesis. Sema4D might be useful as a molecular marker of poor prognosis in cervical cancer.
journal_name
Microvasc Resjournal_title
Microvascular researchauthors
Liu H,Yang Y,Xiao J,Yang S,Liu Y,Kang W,Li X,Zhang Fdoi
10.1016/j.mvr.2014.02.007subject
Has Abstractpub_date
2014-05-01 00:00:00pages
1-8eissn
0026-2862issn
1095-9319pii
S0026-2862(14)00038-7journal_volume
93pub_type
杂志文章abstract::We examined the influence of local cooling (-15 degrees C, 60 sec) on blood flow velocity in nailfold capillaries and on laser Doppler flux (LDF) at the fingertip in 12 patients with primary Raynaud's phenomenon (PRP) and 13 patients with secondary Raynaud's (SRP) in comparison with 10 health controls. Skin temperatur...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.1993.1060
更新日期:1993-11-01 00:00:00
abstract::This study aims to assess the relationship between spontaneous oscillations in changes in cerebral tissue oxyhemoglobin concentrations (Delta [HbO2]) and arterial blood pressure (ABP) signals in healthy elderly subjects during the resting state using wavelet coherence analysis. Continuous recordings of near-infrared s...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2014.02.008
更新日期:2014-05-01 00:00:00
abstract::Leukocyte margination in the vessels of the microcirculation has been attributed to a flow-dependent interaction with red cells. To determine the extent of this effect, experiments with human blood were done in 100- to 180-micron tubes to detect changes in cell distribution as a function of hematocrit and flow rate. U...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/0026-2862(84)90054-2
更新日期:1984-03-01 00:00:00
abstract::Rho-associated kinases are involved in regulation of actin-myosin contractility and the organization of the actin cytoskeleton in both endothelial and smooth muscle cells. By influencing the contraction of the intraendothelial filaments, Rho kinases may affect the size of the interendothelial gaps and thereby influenc...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/s0026-2862(03)00041-4
更新日期:2003-09-01 00:00:00
abstract::Lipopolysaccharide released during bacterial sepsis causes acute lung injury and ARDS. Pulmonary microvascular injury is a feature of ARDS, and vascular remodeling develops, leading to pulmonary hypertension. Pericytes in the lung circulation proliferate and contribute to the remodeling seen in experimental sepsis. It...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.1998.2085
更新日期:1998-09-01 00:00:00
abstract::Despite intensive study in the area of angiogenesis, relatively little is known about normal angiogenesis in adult animals. Preliminary studies using the Griffonia simplicifolia I (GSI) lectin as a microvascular marker indicated that capillary sprouting occurs in the clear "windows" of normal intact adult rat mesenter...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.1994.1029
更新日期:1994-05-01 00:00:00
abstract:OBJECTIVE:To assess the morphology of the lymphatic system pre- and postoperatively in patients undergoing microsurgical reconstructions of the lymphatic vessels. MATERIALS AND METHODS:8 lower extremities in 4 consecutive patients with secondary unilateral lymphedema of the lower extremities were examined by MR lympha...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2008.03.003
更新日期:2008-05-01 00:00:00
abstract::Polymorphonuclear leukocytes are thought to play a pivotal role in the generation of ischemia-reperfusion-induced mucosal injury; however, their behavior in the intestinal microvasculature following this injury has not been directly examined. In this study intravital microscopy was used to investigate the dynamics of ...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.1994.1028
更新日期:1994-05-01 00:00:00
abstract::Interactions between migratory endothelial cells (ECs) and surrounding extracellular matrix (ECM) are of central importance to vascular growth. Here, we present a new model of EC migration and morphogenesis within three-dimensional ECM termed "radial invasion of matrix by aggregated cells" (RIMAC). In the RIMAC model,...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.1998.2122
更新日期:1999-03-01 00:00:00
abstract::An increased recognition of the role of endothelial cells in disease and the development of methods for endothelial cell culture has led to an upsurge in in vitro studies of endothelial cell function. However, the cells most often used for these studies do not reflect the in vivo heterogeneity of endothelial cells. To...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.1997.2045
更新日期:1998-01-01 00:00:00
abstract::The study deals with the adhesion and proliferation of bovine retina pericytes onto surfaces of poly(hydroxymethylsiloxane) (PHMS) modified either by cold plasma or by low-energy ion beams. The surface treatment was able to convert the original polymer matrix into SiO2-like phases for O2-plasma or ion-mixed SiCxOy(Hz)...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2004.08.003
更新日期:2004-11-01 00:00:00
abstract::The purpose of this study was to examine the distribution and extent of autoregulatory behavior among arterioles in the arcade network of the cat mesentery. We found that 71% of 169 arterioles studied dilated and 63% showed blood flow autoregulation with arterial pressure reduction to 55-60 mm Hg. There appeared to be...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/0026-2862(83)90050-x
更新日期:1983-07-01 00:00:00
abstract::During diabetes in rats, the choroid of the eye shows increased permeability to albumin, basement membrane thickening, and decreased anionic charge sites on the abluminal surfaces of the choriocapillary microvessels. In other microvascular beds, permeability differences are correlated with differences in luminal membr...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/0026-2862(91)90058-j
更新日期:1991-11-01 00:00:00
abstract:OBJECTIVE:Qualitative capillaroscopy patterns in juvenile- and adult-onset systemic sclerosis (SSc) were studied in adulthood using data from the EULAR Scleroderma Trials and Research (EUSTAR) database. METHODS:Data collected between June 2004 and April 2013 were examined with focus on capillaroscopy. In this retrospe...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2015.07.007
更新日期:2015-11-01 00:00:00
abstract::Systemic sclerosis (SSc) is a connective tissue disease with high morbidity and mortality, characterized by autoimmunity, obliterative vasculopathy involving mainly the microvasculature, and fibrosis. SSc-specific nailfold capillaroscopic changes have been defined, and nailfold capillaroscopy (NFC) is now unequivocall...
journal_title:Microvascular research
pub_type: 杂志文章,评审
doi:10.1016/j.mvr.2018.03.004
更新日期:2018-07-01 00:00:00
abstract::We tested the hypothesis that the endothelial nitric oxide (NO)-soluble guanylyl cyclase system is involved in atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) mediated regulation of coronary and peripheral vascular resistance. Rat hearts were perfused via the aorta at constant flow and the effect...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.2000.2289
更新日期:2001-01-01 00:00:00
abstract::Mesangium enlargement is a central feature of diabetic nephropathy and almost certainly plays a pathogenic role in this condition. Previous studies have shown that mesangium degradation is reduced in a high glucose mileau. Plasmin has been shown to play an important role in extracellular matrix degradation, both direc...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.1996.2006
更新日期:1997-03-01 00:00:00
abstract::Vascular dysfunction is an important pathophysiologic manifestation of sickle cell disease (SCD), a condition that increases risk of pulmonary hypertension and stroke. We hypothesized that infrared (IR) imaging would detect changes in cutaneous bloodflow reflective of vascular function. We performed IR imaging and con...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2012.06.011
更新日期:2012-11-01 00:00:00
abstract::A cytochemical study of vascular and cellular development in fetal adipose tissue was conducted utilizing 10 plant lectins (fluorescein isothiocyanate (FITC)-labeled), antibodies against laminin, types II and IV collagen, and a probe for actin. Throughout fetal development (50-110 days) blood vessels were stained by g...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/0026-2862(91)90012-z
更新日期:1991-01-01 00:00:00
abstract::Normal brain parenchyma has a highly complex microvascular structure that undergoes re-modelling in the presence of a tumor. A detailed understanding of the clinical and pathological aspects of neo-angiogenesis in malignant human brain tumors is essential in order to ensure the successful clinical application of anti-...
journal_title:Microvascular research
pub_type: 杂志文章,评审
doi:10.1016/j.mvr.2010.09.005
更新日期:2010-12-01 00:00:00
abstract:PURPOSE:The aim of this study was to investigate whether region-dependent endothelial heterogeneity is present within the porcine vortex vein system. METHODS:The superior temporal vortex vein in young adult pig eyes were dissected out and cannulated. The intact vortex vein system down to the choroidal veins was then p...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2013.06.004
更新日期:2013-09-01 00:00:00
abstract::Vessel size index (R(v), μm) has been proposed as a quantitative magnetic resonance imaging (MRI) derived imaging biomarker in oncology, for the non-invasive assessment of tumour blood vessel architecture and vascular targeted therapies. Appropriate pre-clinical evaluation of R(v) in animal tumour models will improve ...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2012.08.001
更新日期:2012-11-01 00:00:00
abstract::In the present study, human myometrial microvascular endothelial cells (HMMEC) were cocultured with human vascular smooth muscle cells (VSMC) labeled with fluorescent dyes to examine their morphological interaction using confocal laser fluorescent microscopy. HMMEC and VSMC labeled with fluorescent green and red dyes,...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2005.04.008
更新日期:2005-07-01 00:00:00
abstract::A large loss of blood during hemorrhage can result in profound shock, a state of hypotension associated with hemodynamic abnormalities. One of the hypotheses to account for this collapse of homeostasis is that the production of nitric oxide (NO), a gas molecule that dilates blood vessels, is significantly impaired dur...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2009.02.009
更新日期:2009-06-01 00:00:00
abstract::In this paper we quantitatively investigate the hypothesis proposed by Michel (Exp. Physiol. 82, 1-30, 1997) and Weinbaum (Ann. Biomed. Eng. 26, 1-17, 1998) that the Starling forces are determined by the local difference in the hydrostatic and colloid osmotic pressure across the endothelial surface glycocalyx, which w...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.1999.2177
更新日期:1999-11-01 00:00:00
abstract::The microcirculation in normal and arthritic juxtaarticular bone was studied in 16 young dogs with carragheenan-induced arthritis of one knee. The regional blood flow was determined by the tissue uptake of intracardially injected 15-microns 141Ce-labeled microspheres, and the microvascular plasma volume was determined...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/0026-2862(90)90020-r
更新日期:1990-09-01 00:00:00
abstract::Studies of blood flow in mesentery, cremaster muscle, and small bore glass tubes were performed to obtain a relationship between mean velocity (Vmean) and red cell velocity using the two-slit method under epifluorescence (Vepi) and transillumination (Vtrans) microscopy. The velocities Vepi and Vtrans obtained in vivo ...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/0026-2862(89)90020-4
更新日期:1989-07-01 00:00:00
abstract::Local skin heating to 42°C causes rapid increases in cutaneous perfusion (initial peak), followed by a brief nadir and subsequent sustained elevation (plateau). Several studies have demonstrated that nitric oxide synthase (NOS) largely contributes to the plateau response during local heating. In this study, we tested ...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2017.12.001
更新日期:2018-05-01 00:00:00
abstract::We investigated the expression of cell adhesion molecules on the surface of glomerular endothelial cells (GEC), dermal microvascular endothelial cells (MvE), and umbilical vein endothelial cells (HUVEC) that had or had not been stimulated by cytokines. PECAM-1 was constitutively expressed at a high level on HUVEC but ...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.2001.2356
更新日期:2001-11-01 00:00:00
abstract::We investigated the kinetics of human mesenchymal stem cells (MSCs) after intravascular administration into SCID mouse cremaster vasculature by intravital microscopy. MSCs were injected into abdominal aorta through left femoral artery at two different concentrations (1 x 10(6) or 0.2 x 10(6) cell). Arterial blood velo...
journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2009.02.001
更新日期:2009-05-01 00:00:00