Vivianne Otto - Academia.edu (original) (raw)

Papers by Vivianne Otto

American Journal of Pathology, Sep 1, 2020

Tumor-associated blood vessels differ from normal vessels and play key roles in tumor progression... more Tumor-associated blood vessels differ from normal vessels and play key roles in tumor progression. We aimed to identify biomolecules that are expressed differentially in human bladder cancereassociated blood vessels to find novel biomarkers and mechanisms involved in tumor-associated angiogenesis. The transcriptome of tumor blood vasculature from human invasive bladder carcinoma (I-BLCA) and normal bladder tissue vasculature was compared using differential expression and unsupervised hierarchical clustering analyses. Pathway analysis identified up-regulation of genes involved in the proliferation, cell cycle, angiogenesis, inflammation, and transforming growth factor-b signaling in tumor blood vasculature. A common consensus gene expression signature was identified between bladder cancer tumor blood vasculature with tumor blood vasculature of other solid cancers, which correlated with the overall survival of patients with several of the solid cancers investigated in The Cancer Genome Atlas data set. In bladder tumor blood vasculature, the secreted factor angiopoietin-like protein 2 (ANGPTL2), was confirmed to be up-regulated by quantitative RT-PCR and immunohistochemical staining. The upregulation of ANGPTL2 in plasma was also observed in non-invasive bladder carcinoma and I-BLCA. We semiquantitatively analyzed expression of ANGPTL2 in tissue microarrays from I-BLCA and surprisingly found an opposite correlation between staining intensity and progression-free survival. Our results indicate that ANGPTL2 might serve as a potential biomarker to predict progression-free survival in I-BLCA.

Journal of Biological Chemistry, 2004

Intercellular adhesion molecule-1 (ICAM-1) occurs as both a membrane and a soluble, secreted glyc... more Intercellular adhesion molecule-1 (ICAM-1) occurs as both a membrane and a soluble, secreted glycoprotein (sICAM-1). ICAM-1 on endothelial cells mediates leukocyte adhesion by binding to leukocyte function associated antigen-1 (LFA-1) and macrophage antigen-1 (Mac-1). Recombinant mouse sICAM-1 induces the production of macrophage inflammatory protein-2 (MIP-2) in mouse astrocytes by a novel LFA-1-and Mac-1-independent mechanism. Here we showed that N-glycan structures of sI-CAM-1 influence its ability to induce MIP-2 production. sICAM-1 expressed in Chinese hamster ovary (CHO) cells was a more potent inducer of MIP-2 production than sI-CAM-1 expressed in HEK 293 cells, suggesting that posttranslational modification of sICAM-1 could influence its signaling activity. To explore the roles of glycosylation in sICAM-1 activity, we expressed sICAM-1 in mutant CHO cell lines differing in glycosylation, including Lec2, Lec8, and Lec1 as well as in CHO cells cultured in the presence of the ␣-mannosidase-I inhibitor kifunensine. Signaling activity of sICAM-1 lacking sialic acid was reduced 3-fold compared with sICAM-1 from CHO cells. The activity of sICAM-1 lacking both sialic acid and galactose was reduced 12-fold, whereas the activity of sICAM-1 carrying only high mannose-type N-glycans was reduced 12-26fold. sICAM-1 glycoforms carrying truncated glycans retained full ability to bind to LFA-1 on leukocytes. Thus, sialylated and galactosylated complex-type N-glycans strongly enhanced the ability of sICAM-1 to induce MIP-2 production in astrocytes but did not alter its binding to LFA-1 on leukocytes. Glycosylation could therefore serve as a means to regulate specifically the signaling function of sICAM-1 in vivo.

Glycobiology, Oct 25, 2002

Journal of Comparative Pathology, 2016

Cancer registries are valuable sources for epidemiological research investigating risk factors un... more Cancer registries are valuable sources for epidemiological research investigating risk factors underlying different types of cancer incidence. The present study is based on the Swiss Feline Cancer Registry that comprises 51,322 feline patient records, compiled between 1965 and 2008. In these records, 18,375 tumours were reported. The study analyses the influence of sex, neutering status, breed, time and age on the development of the most common tumour types and on their locations, using a multiple logistic regression model. The largest differences between breeds were found in the development of fibrosarcomas and squamous cell carcinomas, as well as in the development of tumours in the skin/subcutis and mammary gland. Differences, although often small, in sex and neutering status were observed in most analyses. Tumours were more frequent in middle-aged and older cats. The sample size allowed detailed analyses of the influence of sex, neutering status, breed and age. Results of the study are mainly consistent with previous analyses; however, some results cannot be compared with the existing literature. Further investigations are necessary, since feline tumours have not been investigated in depth to date. More accurate comparisons would require the definition of international standards for animal cancer registries.

Journal of Neurochemistry, 2002

Severe traumatic brain injury stimulates the release of soluble intercellular adhesion molecule-1... more Severe traumatic brain injury stimulates the release of soluble intercellular adhesion molecule-1 (sICAM-1) into CSF. Studies in cultured mouse astrocytes suggest that sICAM-1 induces the production of macrophage inflammatory protein-2 (MIP-2). In the present study, we investigated the underlying mechanisms for MIP-2 induction. sICAM-1 induced MIP-2 in astrocytes lacking membrane-bound ICAM-1, indicating that its action is due to heterophilic binding to an undescribed receptor rather than homophilic binding to surface ICAM-1. Signal transduction may be mediated by src tyrosine kinases, as the src tyrosine kinase inhibitors herbimycin A and PP2 abolished MIP-2 induction by sICAM-1. Phosphorylation of p42/44 mitogen-activated protein kinase (MAPK), but not of p38 MAPK, occurred further downstream, as evidenced by western blot analysis combined with the use of herbimycin A and specific MAPK inhibitors. By contrast, induction of MIP-2 by tumour necrosis factor-alpha (TNF-alpha) involved both p42/44 MAPK and p38 MAPK. Following stimulation with either sICAM-1 or TNF-alpha, astrocyte supernatants promoted chemotaxis of human neutrophils and incubation of these supernatants with anti-MIP-2 antibodies more efficiently suppressed the migration induced by sICAM-1 than by TNF-alpha. These results show that sICAM-1 induces the production of biologically active MIP-2 in astrocytes by heterophilic binding to an undefined receptor and activation of src tyrosine kinases and p42/44 MAPK.

European Journal of Cancer, 2012

Background: This report describes the clinicopathologic findings of six hepatic masses that devel... more Background: This report describes the clinicopathologic findings of six hepatic masses that developed after Kasai hepatic portoenterostomy (HPE) in six patients with longstanding biliary atresia (BA). Methods: Hepatic masses were found in six of 55 pediatric patients who underwent liver transplantation for BA after Kasai HPE from 1997 to 2009. Clinicopathologic analysis was performed and immunohistochemical staining was carried out for CD34, smooth muscle actin (SMA) and cytokeratin 7. Results: Of the six hepatic masses, two were diagnosed as focal nodular hyperplasia (FNH)-like lesions, two were large regenerative nodules (LRN), one was a mesenchymal hamartoma (MH) and one was a cholangiocarcinoma. The immunohistochemical staining findings for SMA and CD34 were more prominent for the FNH-like nodules than for the cirrhotic background liver. Dysplastic biliary epithelium arising from intestinal metaplasia was found in the cholangiocarcinoma. Conclusions: Our findings suggest that FNH-like lesions, LRNs and MH are the results of vascular hemodynamic changes after Kasai HPE and that cholangiocarcinoma is due to recurrent cholangitis after BA. All the lesions in this series must be included in the differential diagnosis of a newly formed hepatic mass in patients after portoenterostomy.

Abstract: Soluble intercellular adhesion molecule-1 (sICAM-1) is elevated in the cerebrospinal fl... more Abstract: Soluble intercellular adhesion molecule-1 (sICAM-1) is elevated in the cerebrospinal fluid of patients with se-vere brain trauma and mouse sICAM-1 induces the production of macrophage inflammatory protein-2 (MIP-2) in mouse astrocytes. The production of MIP-2 is greatly enhanced when sICAM-1 contains sialylated complex-type N-glycans (sICAM-1-CT) as produced by Chinese hamster ovary (CHO) cells. By contrast, sICAM-1 from the Lec1 mutant of CHO cells (sICAM-1-HM), containing only high mannose-type N-glycans, is relatively inactive. Here we show that the N-glycans of sICAM-1-CT are mostly 2,3-sialylated bi-, tri-, and tetraantennary complex-type structures with varying amounts of core fucosylation. Unexpectedly, sICAM-1-CT and sICAM-1-HM bound equivalently to mouse astrocytes. Enhanced MIP-2 induction by sICAM-1-CT was associated with a more rapid, higher level, and prolonged MIP-2 re-sponse as well as sICAM-1-CT accumulation at the plasma membranes of mouse astrocytes. Thes...

The American Journal of Pathology

Glycobiology

Vascular endothelia are covered with a dense glycocalix that is heavily sialylated. Sialylation o... more Vascular endothelia are covered with a dense glycocalix that is heavily sialylated. Sialylation of vascular glycoconjugates is involved in the regulation of cell–cell interactions, be it among endothelial cells at cell junctions or between endothelial and blood-borne cells. It also plays important roles in modulating the binding of soluble ligands and the signaling by vascular receptors. Here, we provide an overview over the sialylation-function relationships of glycoproteins expressed in the blood and lymphatic vasculature. We first describe cellular interactions in which sialic acid contributes in a stereospecific manner to glycan epitopes recognized by glycan-binding proteins. Our major focus is however on the rarely discussed examples of vascular glycoproteins whose biological functions are modulated by sialylation through other mechanisms.

Angewandte Chemie International Edition

Critical thinking in science-isntt his expression am ere tautology?S cience,i ts eems,i sa lways ... more Critical thinking in science-isntt his expression am ere tautology?S cience,i ts eems,i sa lways about critical reflection, is always about inquiring and questioning things rather than taking them simply at face value.But perhaps this is just an ideal?Daily practices may often look very different. There are numerous constraints such as economic needs,f unding and time limits,p eer pressure,a nd ethical concerns.T hese constraints often discourage efforts to critically assess the scientific methods employed, the concepts presupposed, and the conclusions drawn. What we mean by "critical" or "criticism" is the opposite of what might be called "dogmatism" in the sense of using (without questioning) afixed set of methods,concepts,examples,and thereby losing the ability to view things from adistance and from different angles.

Angewandte Chemie

Wasi st neu am sogenannten kritischen Denken? "Kritisches Denken in den Wissenschaften"-das kling... more Wasi st neu am sogenannten kritischen Denken? "Kritisches Denken in den Wissenschaften"-das klingt wie

Oncogene, Jan 22, 2018

Thrombospondin-2 (TSP2) is an anti-angiogenic matricellular protein that inhibits tumor growth an... more Thrombospondin-2 (TSP2) is an anti-angiogenic matricellular protein that inhibits tumor growth and angiogenesis. Tumor-associated blood vascular endothelial cells (BECs) were isolated from human invasive bladder cancers and from matched normal bladder tissue by immuno-laser capture microdissection. Exon expression profiling analyses revealed a particularly high expression of a short TSP2 transcript containing only the last 9 (3') exons of the full-length TSP2 transcript. Using 5' and 3' RACE (rapid amplification of cDNA ends) and Sanger sequencing, we confirmed the existence of the shorter transcript of TSP2 (sTSP2) and determined its sequence which completely lacked the anti-angiogenic thrombospondin type 1 repeats domain. The largest open reading frame predicted within the transcript comprises 209 amino acids and matches almost completely the C-terminal lectin domain of full-length TSP2. We produced recombinant sTSP2 and found that unlike the full-length TSP2, sTSP2 di...

The Journal of pathology, 2017

Bladder cancer is a frequently recurring disease with a very poor prognosis once progressed to in... more Bladder cancer is a frequently recurring disease with a very poor prognosis once progressed to invasive stages, and tumour-associated blood vessels play a crucial role in this process. In order to identify novel biomarkers associated with progression, we isolated blood vascular endothelial cells (BECs) from human invasive bladder cancers and matched normal bladder tissue, and found that tumour-associated BECs greatly up-regulated the expression of insulin receptor (INSR). High expression of INSR on BECs of invasive bladder cancers was significantly associated with shorter progression-free and overall survival. Furthermore, increased expression of the INSR ligand IGF-2 in invasive bladder cancers was associated with reduced overall survival. INSR may therefore represent a novel biomarker to predict cancer progression. Mechanistically, we observed pronounced hypoxia in human bladder cancer tissue, and found a positive correlation between the expression of the hypoxia marker gene GLUT1...

The Journal of Urology, 2015

Mikrofiche-Ausg.: 2 Mikrofiches : 24x Zürich, Eidgenössische Techn. Hochsch., Diss., 1997.