Movement toward the source of a chemoattractant gradient is a basic cellular property in health and disease. Enhanced migration during metastasis involves deregulated growth factor signaling. Growth factor stimulation and cell migration converge both on the important second messenger Ca(2+). To date, the molecular identification of Ca(2+) entry pathways activated by growth factors during chemotaxis is still an open issue. We investigated the involvement of the nonselective Ca(2+) channel TRPC1 (transient receptor potential canonical 1) in FGF-2 guided chemotaxis by means of time-lapse video microscopy and by functional Ca(2+) measurements. To specifically address TRPC1 function in transformed MDCK cells we altered the expression levels by siRNA or overexpression. We report that TRPC1 channels are required for the orientation of transformed MDCK cells in FGF-2 gradients because TRPC1 knockdown or pharmacological blockade prevented chemotaxis. Stimulation with FGF-2 triggered an immediate Ca(2+) influx via TRPC1 channels that depended on phospholipase C and phosphatidylinositol 3-kinase signaling. Impeding this Ca(2+) influx abolished chemotaxis toward FGF-2. This functional connection correlated with clustering of FGF receptors and TRPC1 channels as was observed by immunolabeling. These findings show the important interplay between growth factor signaling and Ca(2+) influx in chemotaxis.
"In spite of still unclear and, possibly, tissue-type dependent role that TRPC1 plays in SOCE, the channel seems to be important for the regulation of cell development and motility, as was demonstrated by knockout or overexpression of TRPC1 in renal epithelial and skeletal muscle cells as well as immortalized GnRH neurons    . Interestingly, while in normal tissue the presence of TRPC1 promotes cell proliferation, in transformed tissues TRPC1 seems to be involved in the regulation of apoptosis. "
[Show abstract][Hide abstract] ABSTRACT: TRP channels form a superfamily of channel proteins exhibiting versatile regulatory characteristics with many channels participating in the regulation of Ca(2+) homeostasis and influencing the cell fate. Multitude of evidence is emerging that the colocalization of TRP channels with Ca(2+)-sensing elements of specific regulatory pathways leading to either proliferation or apoptosis is what makes these channels participate in cell fate regulation and, in turn, determines the final effect of Ca(2+) entry via the particular channel. This review focuses on the aspects of TRP channel localization and function that affect the balance between cell survival and death and how various dysregulations of these channels may lead to perturbed balance and onset of cancer.
[Show abstract][Hide abstract] ABSTRACT: The collector efficiency of upward-type double-pass flat plate solar air heaters with fins attached and external recycle is investigated theoretically. The double-pass device was constructed by inserting the absorbing plate into the air conduit to divide it into two channels (the upper and lower channels). The double-pass device introduced here was designed for creating a solar collector with heat transfer area double as well as the extended area of fins between the absorbing plate and heated air. Moreover, the advantage of external recycle application to solar air heaters is the enhancement of forced heat convection strength, resulting in considerable device heat transfer performance improvement. This advantage may compensate for the remixing at the inlet which decreases the heat transfer transfer-driving force decrement (temperature difference).
International Communications in Heat and Mass Transfer 01/2011; 38(1):49-56. DOI:10.1016/j.icheatmasstransfer.2010.09.015 · 2.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Primary brain tumors, gliomas, diffusely invade the brain by active cell migration either intraparenchymal, along white matter tracts or along blood vessels. The close relationship of glioma with the vasculature assures a continuous supply of oxygen and nutrients essential for cell growth, and exposes cells to a variety growth factors, chemokines, cytokines, and kinins. Signals that attract glioma cells to blood vessels are poorly understood. It has been shown that vascular endothelial cells can initiate the bradykinin (BK) signaling cascade and two bradykinin receptors, B1 and B2, have been identified and cloned. In this study we show that glioma cells isolated from patient biopsies express bradykinin 2 receptors (B2R) whose activation causes intracellular Ca(2+) oscillations. Through time-lapse video-microscopy experiments we show that BK significantly enhances glioma cell migration/invasion. We further show that BK acts as a chemoattractant guiding glioma cells toward blood vessels in acute rat brain slices. The number of cells associated with blood vessels is decreased when B2R are either pharmacologically inhibited or B2R eliminated through short-hairpin RNA knockdown. These data strongly suggest that bradykinin, acting via B2R, acts as an important signal directing the invasion of glioma cells toward blood vessels. A clinically approved B2R antagonist is available that could be used as anti-invasive drug in glioma patients in the future.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 03/2011; 31(13):4858-67. DOI:10.1523/JNEUROSCI.3825-10.2011 · 6.34 Impact Factor
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