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Antitubulin Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Microtubules are highly dynamic cytoskeletal polymers found in all eukaryotic cells. They serve as an essential structural component within the cell and are important for the maintenance of cell shape and polarization (Figure 4.2). They are involved in a number of cellular processes including cytokinesis, mitosis, cell motility, intracellular transport, secretion, and vesicular transport.
Nanomechanical Analysis of Cells from Cancer Patients
Published in Lajos P. Balogh, Nano-Enabled Medical Applications, 2020
Sarah E. Cross, Yu-Sheng Jin, Jianyu Rao, James K. Gimzewski
Recent progress in the study of cancer cell motility and invasion has generated a greater understanding of the mechanical properties involved in malignant transformation. In particular, the dynamic reorganization of the cytoskeleton has become a specific point of interest regarding changes in cell morphology, motility, adhesion and invasion [4, 5]. Techniques for measuring cell adhesion and motility have been established in the laboratory for in vitro analysis of cellular phenotypic events associated with tumour cells. Current cytoskeleton analysis techniques include biochemical purifications, gene expression and polymerization assays, immunofluorescent labelling, and time-lapse and electron microscopies [6, 7]. Recently, a change in the physical properties, in particular cell elasticity, of tissue cells has been recognized as an indication of disease [2, 8, 9] and has emerged as a marker for cellular phenotypic events associated with cell adhesion and cytoskeletal organization [2, 10–12]. In particular, several studies have shown a reduction in stiffness with increasing metastatic efficiency in human cancer cell lines using several different in vitro biomechanical assays [13–15].
Human Keratinocyte Migration Involves Extracellular Matrix and Soluble Factors
Published in John J. Lemasters, Constance Oliver, Cell Biology of Trauma, 2020
David T. Woodley, John D. Chen, Elizabeth Shim, Janice P. Kim, Jean-Christophe Lapiere, Christina Peavey
While reepithelialization involves both cellular motility and cell division, our laboratory has focused on the process of cell motility. Toward this end, we devised a modification of the Albrecht-Buehler track assay for human keratinocytes.1
Heterogeneous Differentiation of Highly Proliferative Embryonal Carcinoma PCC4 Cells Induced by Curcumin: An In Vitro Study
Published in Nutrition and Cancer, 2021
Geetha Viswanathan, Lip Yong Chung, Usha K. Srinivas
Since we observed an enhanced formation of focal adhesions in the differentiated PCC4 cells, there could also be changes in cell motility because these two processes are connected. Lamellipodia and stress bundles are two important organized structures composed of microfilaments that form during cell migration. Actin stress bundles were observed in the differentiated cells (Figure 1B). Manual tracking of the migration paths of individual cells clearly demonstrated that the motility of PCC4 cells gradually increased during curcumin treatment (P < 0.05), reaching a maximum speed after 48 h of treatment (Figure 5C). The track overlays depicted in Figure 5D illustrated the differences between the motility of the untreated control and the curcumin-treated cells at 48 h, and they clearly showed that individual curcumin-treated differentiated cells had longer track overlays compared to the control cells.
Antimetastatic Properties of Tea Polyphenols
Published in Nutrition and Cancer, 2020
Cell motility and migration is essential for organogenesis; however, when regulation fails, it may result in metastasis. Loss of epithelial characteristics (apical– basal polarity, differentiated, organized) and gaining mesenchymal-like cell phenotype are required for the acquisition of motility. It is suggested that the detachment and escaping of cells from the primary tumor mimics the developmental process known as epithelial–mesenchymal transition. An EMT is characterized by loss of cell-junction proteins, e.g., epithelial E-cadherin, an increased expression of mesenchymal markers, such as N-cadherin, vimentin intermediate filaments and fibronectin, loss of cell polarity, and gaining a spindle-shaped form (11,35). E- to N-cadherin expression is known as cadherin-switch that leads to enhanced motility (35). Besides increasing cell motility, EMT also helps to maintain a stem cell property, in suppressing apoptosis, senescence, immune reactions, and to acquire resistance to chemo- and radiotherapy (33). EMT in metastatic cells, however, is transitional (1). EMT is reversed and cells regain epithelial characteristics before they settle down at secondary sites. This phenomenon is known as mesenchymal–epithelial transition (MET). Invasion of metastatic cells occurs through the ECM by different mechanisms. They move either as single cell via mesenchymal cell migration or ameboid cell migration, or move collectively as epithelial sheet.
Novel therapeutic targets for cancer metastasis
Published in Expert Review of Anticancer Therapy, 2020
Konstantin Stoletov, Perrin H. Beatty, John D. Lewis
Integrin-associated tetraspanin CD151 was determined to be necessary for de-adhesion of cancer cells from the solid tumor, which in turn is an essential first step toward cancer cell intravasation and migration to a secondary lesion site [88]. Blocking this tetraspanin with a CD151 monoclonal antibody resulted in a potent inhibition of cancer cell motility and metastasis [5,69]. Furthermore, this provided evidence that targeting and blocking the functionality of a protein required for multiple metastatic stages was a valid therapeutic anti-metastatic approach. However, it also showed the importance of identifying a therapeutic target that is selective for cancer cells over normal cells. Although CD151 inhibition promoted metastatic cancer cell adhesion to its primary tumor, active CD151 is also necessary for host platelet aggregation and keratinocyte migration in wound healing, which makes CD151 a poor cancer therapeutic agent for use in humans [89]. Since that work, additional genes and regulatory factors in cancer cells have now been found that are essential for cell motility.