We experimentally investigate how drying history influences microparticle-substrate adhesion in hydrophilic systems. By systematically varying air temperature, relative humidity, and drying duration under controlled conditions, we quantify the detachment force of individual microparticles. Air temperature emerges as the dominant factor: higher temperatures and lower humidity enhance adhesion, while prolonged drying generally reduces it, except under combined high-temperature and low-humidity conditions, where strong adhesion persists. Complementary scanning electron microscopy (SEM) results reveal drying-time-dependent changes in the particle-substrate contact size, consistent with capillary-induced compression of the contact zone followed by partial relaxation. These findings indicate that transient capillary stresses during evaporation deform the particle-substrate interface and leave a lasting imprint on adhesion strength. Overall, the study shows how capillarity, drying dynamics, and contact mechanics couple to regulate adhesion in colloidal systems, offering new insights into particle-substrate interactions in soft matter contexts.

We explore the potential for air bubble entrapment beneath micrometer-sized particles following immersion. This investigation employs theoretical, numerical, and experimental methodologies, with a focus on the wetting characteristics of both the particle and its substrate. These properties are crucial in determining the likelihood of entrapment and its impact on the particle's adhesion force to the substrate. The theoretical model provides the mathematical framework to account for the additional force exerted on the particle due to the entrapped bubble, while numerical calculations yield corresponding force values. The results underscore the significant influence of the wettability of both the particle and the substrate on this force. In support of findings of the numerical model, companion experiments were performed. The results demonstrate that the bubbles can indeed be entrapped at microscales underneath micrometric particles. Experimental measurements of detachment force reveal the substantial impact of these entrapped bubbles on the force required to detach particles from a surface. Specifically, the force appears notably higher when either the particle or the substrate, or both, exhibit hydrophobic characteristics. We highlight the alignment observed between numerical calculations and experimental results, while also examining and discussing any identified disparities and their root causes. Lastly, we propose an energy model that predicts the post-detachment configuration of the bubble, determining whether it remains attached to the particle, adheres to the substrate, or splits into daughter bubbles distributed across both surfaces. These findings hold significance for a wide range of industrial applications where the immersion of micrometer-sized entities, such as dirt or bacteria, is common during liquid-based cleaning processes.

Expression of concern for ‘Plasmonic photothermal cancer therapy with gold nanorods/reduced graphene oxide core/shell nanocomposites’ by Kostiantyn Turcheniuk et al., RSC Adv., 2016, 6, 1600–1610, https://doi.org/10.1039/C5RA24662H.

There is growing evidence that ion channels are critically involved in cancer cell invasiveness and metastasis. However, the molecular mechanisms of ion signaling promoting cancer behavior are poorly understood and the complexity of the underlying remodeling during metastasis remains to be explored. Here, using a variety of in vitro and in vivo techniques, we show that metastatic prostate cancer cells acquire a specific Na + /Ca 2+ signature required for persistent invasion. We identify the Na + leak channel, NALCN, which is overexpressed in metastatic prostate cancer, as a major initiator and regulator of Ca 2+ oscillations required for invadopodia formation. Indeed, NALCN‐mediated Na + influx into cancer cells maintains intracellular Ca 2+ oscillations via a specific chain of ion transport proteins including plasmalemmal and mitochondrial Na + /Ca 2+ exchangers, SERCA and store‐operated channels. This signaling cascade promotes activity of the NACLN‐colocalized proto‐oncogene Src kinase, actin remodeling and secretion of proteolytic enzymes, thus increasing cancer cell invasive potential and metastatic lesions in vivo . Overall, our findings provide new insights into an ion signaling pathway specific for metastatic cells where NALCN acts as persistent invasion controller.

Cytosolic Ca2+ oscillations provide signaling input to several effector systems of the cell. These include neuronal development, migration and networking. Although similar signaling events are hijacked by highly aggressive cancer cells, the complexity of the ‘neuron-like’ remodeling in metastasis remains to be explored. Here, using a variety of in vitro and in vivo techniques we show that strongly metastatic prostate cancer cells acquire specific Na+/Ca2+ signature required for persistent invasion. We identify the ‘neuronal’ Na+ leak channel, NALCN, at the hot spots of the Ca2+ wave initiation and invadopodia formation. Mechanistically, NALCN associates functionally with plasmalemmal and mitochondrial Na+/Ca2+ exchangers, reactive oxygen species and store-operated channels to generate intracellular Ca2+ oscillations. In turn, this stimulates the activity of protooncogene Src kinase co-localized with NALCN, actin remodeling and secretion of proteolytic enzymes, thus increasing an invasive potential of the cancer cells and metastatic lesions in vivo (accessed in pre-clinical models). Overall, our findings provide new insight into the signaling pathway specific for metastatic cells where NALCN plays the role of the persistent invasion “launcher and controller”.

The characterization of calcium channel interactome in the last decades opened a new way of perceiving ion channel function and regulation. Partner proteins of ion channels can now be considered as major components of the calcium homeostatic mechanisms, while the reinforcement or disruption of their interaction with the channel units now represents an attractive target in research and therapeutics. In this review we will focus on the targeting of calcium channel partner proteins in order to act on the channel activity, and on its consequences for cell and organism physiology. Given the recent advances in the partner proteins' identification, characterization, as well as in the resolution of their interaction domain structures, we will develop the latest findings on the interacting proteins of the following channels: voltage-dependent calcium channels, transient receptor potential and ORAI channels, and inositol 1,4,5-trisphosphate receptor.

Abstract Accruing evidence indicates that exposure to environmental compounds may adversely affect human health and promote carcinogenesis. Triclosan (TCS), an antimicrobial agent widely used as a preservative in personal care products, has been shown to act as an endocrine disruptor in hormone-dependent tissues. Here, we demonstrate a new molecular mechanism by which TCS stimulates the secretion by human prostate cancer stromal cells of vascular endothelial growth factor (VEGF), a factor known to promote tumor growth. This mechanism involves an increase in intracellular calcium levels due to the direct activation of a membrane ion channel. Using calcium imaging and electrophysiology techniques, we show for the first time that environmentally relevant concentrations of TCS activate a cation channel of the TRP family, TRPA1 (Transient Receptor Potential Ankirin 1), in primary cultured human prostate cancer stromal cells. The TCS-induced TRPA1 activation increased basal calcium in stromal cells and stimulated the secretion of VEGF and epithelial cells proliferation. Interestingly, immunofluorescence labeling performed on formalin-fixed paraffin-embedded prostate tissues showed an exclusive expression of the TRPA1 channel in prostate cancer stromal cells. Our data demonstrate an impact of the environmental factor TCS on the tumor microenvironment interactions, by activating a tumor stroma-specific TRPA1 ion channel. Cancer Prev Res; 10(3); 177–87. ©2017 AACR.

Previous studies showed the effects of resveratrol (RES) on several cancer cells, including prostate cancer (PCa) cell apoptosis without taking into consideration the impact of the tumor microenvironment (TME). The TME is composed of cancer cells, endothelial cells, blood cells, and cancer‐associated fibroblasts (CAF), the main source of growth factors. The latter cells might modify in the TME the impact of RES on tumor cells via secreted factors. Recent data clearly show the impact of CAF on cancer cells apoptosis resistance via secreted factors. However, the effects of RES on PCa CAF have not been studied so far. We have investigated here for the first time the effects of RES on the physiology of PCa CAF in the context of TME. Using a prostate cancer CAF cell line and primary cultures of CAF from prostate cancers, we show that RES activates the N‐terminal mutated Transient Receptor Potential Ankyrin 1 (TRPA1) channel leading to an increase in intracellular calcium concentration and the expression and secretion of growth factors (HGF and VEGF) without inducing apoptosis in these cells. Interestingly, in the present work, we also show that when the prostate cancer cells were co‐cultured with CAF, the RES‐induced cancer cell apoptosis was reduced by 40%, an apoptosis reduction canceled in the presence of the TRPA1 channel inhibitors. The present work highlights CAF TRPA1 ion channels as a target for RES and the importance of the channel in the epithelial‐stromal crosstalk in the TME leading to resistance to the RES‐induced apoptosis.

Neuroendocrine cells release their secretion into the extracellular environment through calcium-dependent signalling pathways. These cells share common morphological and molecular features such as the expression of specific biomarkers, neurite outgrowth and dense core secretory granules. In order to elucidate the signalling pathways leading from undifferentiated to differentiated neuroendocrine cells, the role of voltage-dependent calcium channels, central actors in the excitation-secretion coupling, has been comprehensively investigated. T-type calcium channels appear to belong to the most important ion channel family involved in the neuroendocrine differentiation process. They could also participate in the development of neuroendocrine tumours.

Affiliations Univ. Lille, Inserm, U1003 PHYCEL Physiologie Cellulaire, F-59000 Lille, Equipe labellisée par la Ligue Nationale contre le cancer, Villeneuve d’Ascq, France; Laboratory of Excellence, Ion Channels Science and Therapeutics; Université Lille I Sciences et Technologies, Villeneuve d’Ascq, France Laboratoire d’Anatomie et de Cytologie Pathologique du groupement hospitalier de l’Institut Catholique de Lille, Faculté Libre de Médecine, Lille Service d’Urologie de l’hôpital St-Philibert Cardiovascular and Respiratory Studies, The University of Hull, Castle Hill Hospital, Cottingham, Hull HU16 5JQ, UK

Since its cloning a decade ago, TRPM8 channel has emerged as a promising prognostic marker and a putative therapeutic target in prostate cancer (PCa). However, recent studies have brought to light the complexity of TRPM8 isoforms in PCa. Consequently, the respective role of each TRPM8 isoform needs to be deciphered prior to considering TRPM8 as an attractive therapeutic target. Full-length (6 transmembrane (TM)-domain) TRPM8 channel is overexpressed in early PCa and repressed in advanced prostate tumors whereas the localization of the truncated, 4TM-TRPM8 channel (4 transmembrane (TM)-domain), in the membranes of endoplasmic reticulum (ER) is independent of the pathogenic status of epithelial cells. In the same line, expression of non-channel cytoplasmic small TRPM8 isoforms (namely sM8) is conserved in cancer cells. In this study, we identify sM8s as putative regulator of PCa cell death. Indeed, suppression of sM8 isoforms was found to induce concomitantly ER stress, oxidative stress, p21 expression and apoptosis in human epithelial prostate cancer cells. We furthermore demonstrate that induction of such mechanisms required the activity of 4TM-TRPM8 channels at the ER-mitochondria junction. Our study thus suggests that targeting sM8 could be an appropriate strategy to fight prostate cancer.

photothermal therapy (PPTT) has become a powerful tool for elimination of pathogenic tissues, e.g. tumor growths. To achieve such PPTT applications, however, the nanocomposite structures need to be strictly controlled. Ideally, nanocomposites should have the following traits: (1) efficient absorption and conversion of photon energy into heat, (2) a targeting component, and (3) a capacity to be visualized easily in vivo. Gold nanorods (Au NRs) are known for their ability to convert photon energy into heat efficiently, resulting in hyperthermia, and thus a suppression of tumor growth in vitro and in vivo. Wrapping gold nanostructures in reduced graphene oxide (rGO) greatly enhances their light-to-heat conversion under NIR (808 nm) irradiation.1 We have recently reported2 the creation of Au NRs covered with rGO, which were additionally conjugated with TAT peptide to ensure selective targeting of human astrocytoma U87MG tumor cells,3 and with commercially available Cy7-NHS NIR dye to ensure visualization on nanocomposites in vivo. The resulting Au NRs@rGO-PEG-Tat/Cy7 nanocomposites were used for PPTT of Swiss nude mice with model U87MG-originating tumors. In vivo and ex vivo Fluorescence Imaging of Functionalized Gold/Graphene Nanocomposites during Plasmonic Photothermal Therapy in Mice

Gold nanorods (Au NRs) are known for their efficient conversion of photon energy into heat, resulting in hyperthermia and suppression of tumor growths in vitro and in vivo.

Sodium (Na+) ions are known to regulate many signaling pathways involved in both physiological and pathological conditions. In particular, alterations in intracellular concentrations of Na+ and corresponding changes in membrane potential are known to be major actors of cancer progression to metastatic phenotype. Though the functionality of Na+ channels and the corresponding Na+ currents can be investigated using the patch-clamp technique, the latter is rather invasive and a technically difficult method to study intracellular Na+ transients compared to Na+ fluorescence imaging. Despite the fact that Na+ signaling is considered an important controller of cancer progression, only few data using Na+ imaging approaches are available so far, suggesting the persisting challenge within the scientific community. In this study, we describe in detail the approach for application of Na+ imaging technique to measure intracellular Na+ variations in human prostate cancer cells. Accordingly, we used three Na+-specific fluorescent dyes–Na+-binding benzofuran isophthalate (SBFI), CoroNa™ Green (Corona) and Asante NaTRIUM Green-2 (ANG-2). These dyes have been assessed for optimal loading conditions, dissociation constant and working range after different calibration methods, and intracellular Na+ sensitivity, in order to determine which probe can be considered as the most reliable to visualize Na+ fluctuations in vitro.

Objective: Endothelin-1 (ET-1), a potent vasoconstrictor secreted primarily by endothelial and various epithelial cancer cells has been implicated in prostate cancer progression and the ET axis has been suggested to represent a novel and exciting target in the treatment of prostate cancer (PCa). ET-1, acting primarily through the endothelin receptors (ETRs) is integrally involved in multiple facets of PCa progression, including cell growth, inhibition of apoptosis, angiogenesis and development of bone metastases. ET-1 and ETRs are expressed in PCa tissues and their expression is modulated during the evolution of these cancers. The purpose of the present work was to study the effects of ET-1 on proliferation of human PCa cells PC-3 and the mechanisms by which the activation of ETRs may promote the PCa cells growth. Methods: Prostate cancer cell lines and primary cultured epithelial cells from prostate cancer, RT-PCR and calcium imaging techniques were used to study the expression and functionality of the Endothelin receptors and involvement of ion channels in the effects of ET-1 in prostate cancer cells. Results: We show for the first time that the application of ET-1 induces a dose-dependent cell proliferation and an increase in intracellular free Ca2+ concentrations ([Ca2+]i) via a mobilisation of the internal calcium stores and by a capacitative calcium entry (CCE). These effects of ET-1 were completely abolished by BQ123, a selective ETAR antagonist, but not by BQ788, a selective ETBR antagonist. By use of pharmacological inhibitors and siRNA targeting calcium-activated (IKCa1 and BKCa) potassium channels and calcium channels (TRPC1, TRPV6, Orai1), we showed that these ion channels play an important role in calcium entry and cell proliferation induced by ET-1 in PCa cells. Conclusion: These results suggest that these ions channels evidenced here might constitute potential targets to block the ET axis in human prostate cancers.

In the present study, we have assessed whether a putative calcium channel α2δ2 auxiliary subunit (CACNA2D2 gene) could be involved in prostate cancer (PCA) progression. We therefore carried out experiments to determine whether this protein is expressed in PCA LNCaP cells and in PCA tissues, and whether its expression may be altered during cancer development. In addition, we evaluated the influence on cell proliferation of overexpressing or downregulating this subunit. In vitro experiments show that α2δ2 subunit overexpression is associated with increased cell proliferation, alterations of calcium homeostasis and the recruitment of a nuclear factor of activated T-cells pathway. Furthermore, we carried out in vivo experiments on immuno-deficient nude mice in order to evaluate the tumorigenic potency of the α2δ2 subunit. We show that α2δ2-overexpressing PCA LNCaP cells are more tumorigenic than control LNCaP cells when injected into nude mice. In addition, gabapentin, a ligand of α2δ2, reduces tumor development in LNCaP xenografts. Finally, we show that the action of α2δ2 on tumor development occurs not only through a stimulation of proliferation, but also through a stimulation of angiogenesis, via an increased secretion of vascular endothelial growth factor in cells overexpressing α2δ2.

Defects in the human protein TMEM165 are known to cause a subtype of Congenital Disorders of Glycosylation. Transmembrane protein 165 (TMEM165) belongs to an uncharacterized family of membrane proteins called Uncharacterized Protein Family 0016, which are well conserved throughout evolution and share characteristics reminiscent of the cation/Ca 2+ exchanger superfamily. Gcr1 dependent translation factor 1 (Gdt1p), the budding yeast member of this family, contributes to Ca 2+ homeostasis via an uncharacterized Ca 2+ transport pathway localized in the Golgi apparatus. The gdt1Δ mutant was found to be sensitive to high concentrations of Ca 2+ , and interestingly, this sensitivity was suppressed by expression of TMEM165, the human ortholog of Gdt1p, indicating conservation of function among the members of this family. Patch-clamp analyses on human cells indicated that TMEM165 expression is linked to Ca 2+ ion transport. Furthermore, defects in TMEM165 affected both Ca 2+ and pH homeostasis. Based on these results, we propose that Gdt1p and TMEM165 could be members of a unique family of Golgi-localized Ca 2+ /H + antiporters and that modification of the Golgi Ca 2+ and pH balance could explain the glycosylation defects observed in TMEM165-deficient patients.