Authors: Scolz, M.; Widlund, P.O.; Piazza, S.; Bublik, D.R.; Reber, S.; Peche, L.Y.; Ciani, Y.; Hubner, N.; Isokane, M.; <div class="autor_fcen" id="5899">Monte, M.</div>; Ellenberg, J.; Hyman, A.A.; Schneider, C.; Bird, A.W.
Publication Date: 2012.
The regulation of cell migration is a highly complex process that is often compromised when cancer cells become metastatic. The microtubule cytoskeleton is necessary for cell migration, but how microtubules and microtubule-associated proteins regulate multiple pathways promoting cell migration remains unclear. Microtubule plus-end binding proteins (+TIPs) are emerging as important players in many cellular functions, including cell migration. Here we identify a +TIP, GTSE1, that promotes cell migration. GTSE1 accumulates at growing microtubule plus ends through interaction with the EB1+TIP. The EB1-dependent +TIP activity of GTSE1 is required for cell migration, as well as for microtubule-dependent disassembly of focal adhesions. GTSE1 protein levels determine the migratory capacity of both nontransformed and breast cancer cell lines. In breast cancers, increased GTSE1 expression correlates with invasive potential, tumor stage, and time to distant metastasis, suggesting that misregulation of GTSE1 expression could be associated with increased invasive potential. © 2012 Scolz et al.
Author affiliation: Monte, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Keywords: binding protein; end binding 1 protein; G2 and S phase expressed 1 protein; microtubule associated protein; microtubule plus end tracking protein; microtubule protein; unclassified drug; article; breast cancer; cancer cell culture; cell migration; controlled study; focal adhesion; human; human cell; microtubule; nucleotide sequence; protein function; protein protein interaction; regulatory mechanism; Breast Neoplasms; Cell Line; Cell Movement; DNA Primers; Female; Fluorescent Antibody Technique; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immunoprecipitation; Kaplan-Meier Estimate; Mass Spectrometry; Microscopy, Fluorescence; Microtubule-Associated Proteins; Microtubules; Neoplasm Invasiveness; Real-Time Polymerase Chain Reaction; RNA Interference; RNA, Small Interfering.
Repository: Biblioteca Digital (UBA-FCEN). Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
Publication Date: 2012.
Two liposomal formulations of doxorubicin (Caelyx® and Doxopeg®) were evaluated for phospholipid content, doxorubicin concentration, liposomal size, zeta potential, osmolarity, phospholipid peroxidation, in vitro release of the drug, pharmacokinetic profile, and cytotoxicity in cancer cell cultures. Phospholipid concentration was not statistically different between formulations. Doxorubicin concentration was in the range of 2.0 mg/mL. Size and zeta potential were in the order of 80 nm and -37 mV, respectively. Osmolarity and peroxidation in both formulations was similar and the in vitro drug release assay indicated minimal release (2 %) of the doxorubicin content after 48 h. Pharmacokinetics parameters in both formulations were very similar and no statistical difference was observed between them; the effect on the growth inhibition in cell lines was also not different. Caelyx® and Doxopeg® are similar in terms of its composition, physical parameters, stability, pharmacokinetics and growth inhibition in cancer cell lines.
Colegio de Farmacéuticos de la Provincia de Buenos Aires
Repository: SEDICI (UNLP). Universidad Nacional de La Plata