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The Anticancer Potential of the Bacterial Protein Azurin and Its Derived Peptide p28
Published in Ananda M. Chakrabarty, Arsénio M. Fialho, Microbial Infections and Cancer Therapy, 2019
Ana Rita Garizo, Nuno Bernardes, Ananda M. Chakrabarty, Arsénio M. Fialho
In 2013, a study assessed the activity of MMP-2 by gelatin zymography in the conditioned media of these breast cancer cells treated with azurin and observed a decrease in its activity. In the same study, it was observed that the decrease in P-cadherin caused by azurin was parallel to a decrease in the phosphorylated levels of FAK and Src nonreceptor proteins, without any alteration in total FAK and Src protein levels (Figs 9.3 and 9.4). It is known that FAK is necessary to the regulation of invadopodia in ovarian carcinoma cells and to promote breast cancer cell invasion [15]. Additionally, in v-Src-transformed fibroblast cells, FAK promotes the formation of a v-Src-Cas-Crk-Dock180 complex, which leads to an elevated expression of MMP-2 and MMP-9 [43]. Also Src, when activated, can facilitate motility and invasion through reorganization of the actin cytoskeleton and disruption of normal cell–cell and cell–matrix adhesion [44].
Structure and function of the mesothelial cell
Published in Wim P. Ceelen, Edward A. Levine, Intraperitoneal Cancer Therapy, 2015
Steven E. Mutsaers, Cecilia M. Prêle, Sarah E. Herrick
A recent study by Satoyoshi et al. [149], using human tissue and a mouse model of scirrhous gastric cancer, suggests that peritoneal mesothelial cells in peritoneal carcinomatosis undergo MMT and acquire invasive properties and then guide the invasion of cancer cells. They showed that Tks5, an adaptor protein required for podosome and invadopodia formation by certain cells and a substrate for Src family kinases, was upregulated in mesothelial cells exposed to cancer cells. If Tks5 was blocked, invasion did not occur. Likewise, if Tks5 expression was reinstated, invasion progressed. This is an important finding as it shows that mesothelial cells can be “hijacked” by cancer cells to support their invasion and growth.
Angiogenesis and Roles of Adhesion Molecules in Psoriatic Disease
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Asmita Hazra, Saptarshi Mandal
The initiation of angiogenesis generally involves sensing of the angiogenic stimulus formed by a shift in the balance of the local vessel homeostatic milieu toward a “pro-angiogenic” state. The angiogenic signal can be a rapid release of pre-stored and sequestered molecules, or local new synthesis and secretion of agonists as, for example, growth factors like VEGFs, angiopoietins, FGFs, and other signaling molecules like chemokines, alarmins, and so forth. The release can be from a dormant state bound to the ECM or from storage granules of cells that may concentrate them, for example, mast cells, neutrophils, and platelets. Inflammatory cells, especially myeloid cells, described later, can play the role of the vessel destabilization event, as well as an angiogenic signal generation event or its amplification. Whatever the route of initiation, the endothelial activation involves turning on an “angiogenic switch” (cooperative molecular on–off event rather than a gradual event) in the endothelial cells, which amplify and maintain the expression of the players of the angiogenic cascade. The sprouting part of the angiogenesis has many mechanistic similarities to epithelial-to-mesenchymal transition (EMT) and has been dubbed endothelial-to-mesenchymal transition (EndMT) and is mediated partly by the Snail/Slug family of transcription factors, which are Notch and NFkB targets. The sprouting endothelial cells invade the basement membrane through adhesive podosomes, which are similar to the invadopodia of cancerous cells. A parallel cascade of events is set in the associated stromal cells, some of which may eventually differentiate into the pericytes and other mural cells during the growth or stabilization of the sprouts.
Polygenic risk for traumatic loss-related PTSD in US military veterans: Protective effect of secure attachment style
Published in The World Journal of Biological Psychiatry, 2021
Ruth H. Asch, Irina Esterlis, Frank R. Wendt, Lorig Kachadourian, Steven M. Southwick, Joel Gelernter, Renato Polimanti, Robert H. Pietrzak
In our exploratory PTSDREX PRS gene set enrichment analysis, the strongest result was observed for genes involved in podosome cellular structure. Genes involved in invadopodium structure and function (GO: 0071437) also emerged. Podosomes and invadopodia are microglial structures that mediate inflammatory responses and matrix remodelling following disease or injury (Vincent et al. 2012). Podosomes and invadopodia are further implicated neuron motility and neurite outgrowth, thereby influencing neurodevelopment and plasticity (Tanna et al. 2019). Although no known studies have investigated the role of these cellular structures in PTSD pathogenesis, a recent multivariate gene-by-environment genome–wide interaction study in >120,000 UK Biobank participants identified extracellular matrix biology and synaptic plasticity as biological mediators of the effects of PTSD and trauma on genetic risk for suicidal behaviour (Wendt et al. 2020). Taken together, these findings suggest a need for further study into the possible role of extracellular matrix and glial structural elements in the pathophysiology of PTSD (Bach et al. 2019).
The therapeutic effects of blocking IGF-R1 on mice model of skin cancer
Published in Journal of Dermatological Treatment, 2021
Matrix metalloproteases (MMP) plays a crucial role in tumor proliferation, invasion and metastasis. It is has the ability to hydrolyze the major compound in the basement membrane, type IV collagen (23). Moreover, it destructed the basement membranes in blood vessels as well as is engaged in angiogenesis and neovascularization (24). MMP9 helps in the proteolytic conversion of syndecan-1 to be a soluble molecule instead of membrane bound enhancing tumor metastasis. Syndecan-1 possesses the ability to interact with extracellular matrix growth factors such as fibroblast growth factor (FGF) family leading to antigenic stimulation (25). In addition, fascin-1, actin-binding protein, is highly expressed in many cancers such as skin, lung, breast, colon cancers and leukemia. It established the formation of invadopodia in cancer cells (26). Upregulation of fascin causes modifications in the cytoskeleton altering extracellular matrix and enhances tumor metastasis. However, blocking or knocking down of fascin-1 blocked the migration and invasion ability of cancer cells in some cancer types such as hepatocellular carcinoma (27). In skin cancer, fascin is reported to be over expressed leading to locally infiltrate and substitutes the surrounding tissues affecting cell–cell and cell–matrix interaction, enhancing cell adhesion, motility and invasiveness increasing the risk of metastasis (28). However, we found significant increase in the gene and protein expression of MMP9, syndecan-1 and fascin-1 in skin cancer, which are attenuated by treating cancer mice with PQ401 without affecting the control mice.
Subtypes of tumour cell-derived small extracellular vesicles having differently externalized phosphatidylserine
Published in Journal of Extracellular Vesicles, 2019
Sachiko Matsumura, Tamiko Minamisawa, Kanako Suga, Hiromi Kishita, Takanori Akagi, Takanori Ichiki, Yuki Ichikawa, Kiyotaka Shiba
Recently, the protruded structures of cells, such as cilia, microvilli, filopodia, podosomes, retraction fibres, and invadopodia, have garnered attention as sources of EV secretion [46,50–52]. Among them, invadopodia is a cancer cell-specific structure that is involved in tumour cell invasion and has been reported to be associated with enhanced secretion of EVs [52]. Because malignant tumour-derived cell lines were used in this study, vesicles generated from invadopodia could be included in the sEV preparations. Indeed, β-actin and Src, which are enriched in invadopodia (and some other protruded structures) were found from low-density sEVs, canonical exosomes, and high-density sEV fractions (Figure S2(a)). Interestingly, the activated form of Src (pY416-Src) was absent in the low-density sEVs but noticeable in the high-density fraction, suggesting different biological roles of these three subtypes, for example, on cell migration. Because most protruded structures are associated with β-actin, further studies are needed to determine the origin of these β-actin and/or Src-enriched subtypes of sEVs.