Université de Fribourg

Absence of calretinin protein expression in malignant mesotheliomas from asbestos-exposed NF2+/− mice and mouse mesothelioma cell lines from various mouse strains

Blum, Walter ; Henzi, Thomas ; Châtel-Soulet, Hugues-Etienne ; Pecze, Laszlo ; Wörthmüller Rodriguez, Janine ; Vrugt, Bart ; Schwaller, Beat

In: Biomarker Research, 2018, vol. 6, no. 1, p. 19

Calretinin is the most widespread positive marker for the immunohistochemical identification of malignant mesothelioma (MM) and was proposed to serve as a blood- based biomarker. Functionally, evidence has accumulated that calretinin might be implicated in MM tumorigenesis. We aimed to identify calretinin (CR; Calb2) in murine MM and reactive mesothelial cells in granuloma from...

Université de Fribourg

Regulation of calretinin in malignant mesothelioma is mediated by septin 7 binding to the CALB2 promoter

Blum, Walter ; Pecze, László ; Wörthmüller Rodriguez, Janine ; Steinauer, Martine ; Schwaller, Beat

In: BMC Cancer, 2018, vol. 18, p. 475

The calcium-binding protein calretinin (gene name: CALB2) is currently considered as the most sensitive and specific marker for the diagnosis of malignant mesothelioma (MM). MM is a very aggressive tumor strongly linked to asbestos exposure and with no existing cure so far. The mechanisms of calretinin regulation, as well as its distinct function in MM are still poorly understood.

Université de Fribourg

Putative cancer stem cells may be the key target to inhibit cancer cell repopulation between the intervals of chemoradiation in murine mesothelioma

Wu, Licun ; Blum, Walter ; Zhu, Chang-Qi ; Yun, Zhihong ; Pecze, Laszlo ; Kohno, Mikihiro ; Chan, Mei-Lin ; Zhao, Yidan ; Felley-Bosco, Emanuela ; Schwaller, Beat ; Perrot, Marc de

In: BMC Cancer, 2018, vol. 18, p. 471

Cancer cell repopulation during chemotherapy or radiotherapy is a major factor limiting the efficacy of treatment. Cancer stem cells (CSC) may play critical roles during this process. We aim to demonstrate the role of mesothelioma stem cells (MSC) in treatment failure and eventually to design specific target therapies against MSC to improve the efficacy of treatment in malignant mesothelioma.

Université de Fribourg

How asbestos drives the tissue towards tumors: YAP activation, macrophage and mesothelial precursor recruitment, RNA editing, and somatic mutations

Rehrauer, Hubert ; Wu, Licun ; Blum, Walter ; Pecze, Lazslo ; Henzi, Thomas ; Serre-Beinier, Véronique ; Aquino, Catherine ; Vrugt, Bart ; Perrot, Marc de ; Schwaller, Beat ; Felley-Bosco, Emanuela

In: Oncogene, 2018, vol. 37, no. 20, p. 2645–2659

Chronic exposure to intraperitoneal asbestos triggered a marked response in the mesothelium well before tumor development. Macrophages, mesothelial precursor cells, cytokines, and growth factors accumulated in the peritoneal lavage. Transcriptome profiling revealed YAP/TAZ activation in inflamed mesothelium with further activation in tumors, paralleled by increased levels of cells with...

Université de Fribourg

Biological noise and positional effects influence cell stemness

Blum, Walter ; Henzi, Thomas ; Schwaller, Beat ; Pecze, László

In: Journal of Biological Chemistry, 2018, vol. 293, no. 14, p. 5247–5258

Biological (or cellular) noise is the random quantitative variability of proteins and other molecules in individual, genetically identical cells. As the result of biological noise in the levels of some transcription factors that determine a cell's differentiation status, differentiated cells may dedifferentiate to a stem cell state given a sufficiently long time period. Here, to provide...

Université de Fribourg

Menthol evokes Ca2+ signals and induces oxidative stress independently of the presence of TRPM8 (menthol) receptor in cancer cells

Nazıroğlu, Mustafa ; Blum, Walter ; Jósvay, Katalin ; Çiğ, Bilal ; Henzi, Thomas ; Oláh, Zoltán ; Vizler, Csaba ; Schwaller, Beat ; Pecze, László

In: Redox Biology, 2018, vol. 14, p. 439–449

Menthol is a naturally occurring monoterpene alcohol possessing remarkable biological properties including antipruritic, analgesic, antiseptic, anti-inflammatory and cooling effects. Here, we examined the menthol-evoked Ca2+ signals in breast and prostate cancer cell lines. The effect of menthol (50–500µM) was predicted to be mediated by the transient receptor potential ion channel...

Université de Fribourg

Parvalbumin-expressing ependymal cells in rostral lateral ventricle wall adhesions contribute to aging-related ventricle stenosis in mice

Filice, Federica ; Celio, Marco R. ; Babalian, Alexandre ; Blum, Walter ; Szabolcsi, Viktoria

In: Journal of Comparative Neurology, 2017, vol. 525, no. 15, p. 3266–3285

Aging-associated ependymal-cell pathologies can manifest as ventricular gliosis, ventricle enlargement, or ventricle stenosis. Ventricle stenosis and fusion of the lateral ventricle (LV) walls is associated with a massive decline of the proliferative capacities of the stem cell niche in the affected subventricular zone (SVZ) in aging mice. We examined the brains of adult C57BL/6 mice and...

Université de Fribourg

Targeting breast cancer cells by MRS1477, a positive allosteric modulator of TRPV1 channels

Nazıroğlu, Mustafa ; Çiğ, Bilal ; Blum, Walter ; Vizler, Csaba ; Buhala, Andrea ; Marton, Annamária ; Katona, Róbert ; Jósvay, Katalin ; Schwaller, Beat ; Oláh, Zoltán ; Pecze, László

In: PLOS ONE, 2017, vol. 12, no. 6, p. e0179950

There is convincing epidemiological and experimental evidence that capsaicin, a potent natural transient receptor potential cation channel vanilloid member 1 (TRPV1) agonist, has anticancer activity. However, capsaicin cannot be given systemically in large doses, because of its induction of acute pain and neurological inflammation. MRS1477, a dihydropyridine derivative acts as a positive...

Université de Fribourg

Stem cell factor-based identification and functional properties of in vitro-selected subpopulations of malignant mesothelioma cells

Blum, Walter ; Pecze, , László ; Felley-Bosco, Emanuela ; Wu, Licun ; Perrot, Marc de ; Schwaller, Beat

In: Stem Cell Reports, 2017, vol. 8, no. 4, p. 1005–1017

Malignant mesothelioma (MM) is an aggressive neoplasm characterized by a poor patient survival rate, because of rapid tumor recurrence following first-line therapy. Cancer stem cells (CSCs) are assumed to be responsible for initiating tumorigenesis and driving relapse after therapeutic interventions. CSC-enriched MM cell subpopulations were identified by an OCT4/SOX2 reporter approach and...

Université de Fribourg

Endogenous TRPV1 stimulation leads to the activation of the inositol phospholipid pathway necessary for sustained Ca2+ oscillations

Pecze, László ; Blum, Walter ; Henzi, Thomas ; Schwaller, Beat

In: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2016, vol. 1863, no. 12, p. 2905–2915

Sensory neuron subpopulations as well as breast and prostate cancer cells express functional transient receptor potential vanilloid type 1 (TRPV1) ion channels; however little is known how TRPV1 activation leads to biological responses. Agonist-induced activation of TRPV1 resulted in specific spatiotemporal patterns of cytoplasmic Ca²⁺ signals in breast and prostate cancer-derived cells....