Université de Fribourg

Extending the mathematical palette for developmental pattern formation: piebaldism

Dougoud, Michaël ; Mazza, Christian ; Schwaller, Beat ; Pecze, László

In: Bulletin of Mathematical Biology, 2019, vol. 81, no. 5, p. 1461–1478

Here, we present a theoretical investigation with potential insights on developmental mechanisms. Three biological factors, consisting of two diffusing factors and a cell- autonomous immobile transcription factor are combined with different feedback mechanisms. This results in four different situations or fur patterns. Two of them reproduce classical Turing patterns: (1) regularly spaced...

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

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

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

Molecular surgery concept from bench to bedside: a focus on TRPV1+ pain-sensing neurons

Pecze, László ; Viskolcz, Béla ; Oláh, Zoltán

In: Frontiers in Physiology, 2017, vol. 8, p. -

“Molecular neurosurgery” is emerging as a new medical concept, and is the combination of two partners: (i) a molecular neurosurgery agent, and (ii) the cognate receptor whose activation results in the selective elimination of a specific subset of neurons in which this receptor is endogenously expressed. In general, a molecular surgery agent is a selective and potent ligand, and the target...

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....

Université de Fribourg

Activation of endogenous TRPV1 fails to induce overstimulation-based cytotoxicity in breast and prostate cancer cells but not in pain-sensing neurons

Pecze, László ; Jósvay, Katalin ; Blum, Walter ; Petrovics, György ; Vizler, Csaba ; Oláh, Zoltán ; Schwaller, Beat

In: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2016, vol. 1863, no. 8, p. 2054–2064

Vanilloids including capsaicin and resiniferatoxin are potent transient receptor potential vanilloid type 1 (TRPV1) agonists. TRPV1 overstimulation selectively ablates capsaicin-sensitive sensory neurons in animal models in vivo. The cytotoxic mechanisms are based on strong Na⁺ and Ca2 + influx via TRPV1 channels, which leads to mitochondrial Ca2 + accumulation and...

Université de Fribourg

Routes of Ca²⁺ shuttling during Ca²⁺ oscillations FOCUS ON THE ROLE OF MITOCHONDRIAL Ca²⁺ HANDLING AND CYTOSOLIC Ca²⁺ BUFFERS

Pecze, László ; Blum, Walter ; Schwaller, Beat

In: Journal of Biological Chemistry, 2015, vol. 290, no. 47, p. 28214–28230

In some cell types, Ca²⁺ oscillations are strictly dependent on Ca²⁺ influx across the plasma membrane, whereas in others, oscillations also persist in the absence of Ca²⁺ influx. We observed that, in primary mesothelial cells, the plasmalemmal Ca²⁺ influx played a pivotal role. However, when the Ca²⁺ transport across the plasma membrane by the “lanthanum insulation method” was...

Université de Fribourg

Overexpression or absence of calretinin in mouse primary mesothelial cells inversely affects proliferation and cell migration

Blum, Walter ; Pecze, László ; Felley-Bosc, Emanuela

In: Respiratory Research, 2015, vol. 16, p. 153

The Ca2+-binding protein calretinin is currently used as a positive marker for identifying epithelioid malignant mesothelioma (MM) and reactive mesothelium, but calretinin’s likely role in mesotheliomagenesis remains unclear. Calretinin protects immortalized mesothelial cells in vitro from asbestos-induced cytotoxicity and thus might be implicated in mesothelioma formation. To further...