Francesca Lessi, Paolo Aretini, Milena Rizzo, Mariangela Morelli, Michele Menicagli, Sara Franceschi, Chiara Maria Mazzanti
{"title":"Analysis of exosome-derived microRNAs reveals insights of intercellular communication during invasion of breast, prostate and glioblastoma cancer cells.","authors":"Francesca Lessi, Paolo Aretini, Milena Rizzo, Mariangela Morelli, Michele Menicagli, Sara Franceschi, Chiara Maria Mazzanti","doi":"10.1080/19336918.2021.1935407","DOIUrl":"10.1080/19336918.2021.1935407","url":null,"abstract":"<p><p>MiRNAs represent a mechanism that regulates gene expression in many pathological conditions. Exosomes are known to be secreted from all types of cells, and the exosomes-released molecules are crucial messengers that can regulate cellular processes. We investigated the miRNAs content of exosomes released by cancer cells during the invasion . An invasion stimulus has been generated through scratches created on the confluent cells of cancer cell lines: glioblastoma, breast and prostate cancers.Several miRNAs were found to be significantly differentially abundant during the cell invasion , both in common among different cell lines and exclusive. Understanding the language codes among cells involved in invasion can lead to the development of therapies that can inhibit cellular communication, slowing or eventually stopping their activity.</p>","PeriodicalId":9680,"journal":{"name":"Cell Adhesion & Migration","volume":"15 1","pages":"180-201"},"PeriodicalIF":3.2,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336918.2021.1935407","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39097492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of laminin and cognate receptors in cholangiocarcinoma cell migration.","authors":"Kittiya Islam, Parichut Thummarati, Pakkanun Kaewkong, Banchob Sripa, Tuangporn Suthiphongchai","doi":"10.1080/19336918.2021.1924422","DOIUrl":"https://doi.org/10.1080/19336918.2021.1924422","url":null,"abstract":"<p><p>Extensive desmoplasia in cholangiocarcinoma (CCA) is associated with tumor aggressiveness, indicating a need for further understanding of CCA cell-matrix interaction. This study demonstrated laminin as the most potent attractant for CCA cell migration and the vast elevation of its receptor integrin β4 (ITGB4) in CCA cell lines. Besides, their high expressions in CCA tissues were correlated with lymphatic invasion and the presence of ITGB4 was also associated with short survival time. ITGB4 silencing revealed it as the receptor for laminin-induced HuCCA-1 migration, but KKU-213 utilized 37/67-kDa laminin receptor (LAMR) instead. These findings highlight the role of ITGB4 and LAMR in transducing laminin induction of CCA cell migration and the potential of ITGB4 as diagnostic and prognostic biomarkers for CCA.</p>","PeriodicalId":9680,"journal":{"name":"Cell Adhesion & Migration","volume":"15 1","pages":"152-165"},"PeriodicalIF":3.2,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336918.2021.1924422","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39000750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"P21-activated kinase regulates oxygen-dependent migration of vascular endothelial cells in monolayers.","authors":"Satomi Hirose, Yugo Tabata, Kazuki Sone, Naoyuki Takahashi, Daisuke Yoshino, Kenichi Funamoto","doi":"10.1080/19336918.2021.1978368","DOIUrl":"https://doi.org/10.1080/19336918.2021.1978368","url":null,"abstract":"<p><p>The collective migration of vascular endothelial cells plays important roles in homeostasis and angiogenesis. Oxygen concentration <i>in vivo</i>, which is lower than in the atmosphere and changes due to diseases, is a key factor affecting the cellular dynamics of vascular endothelial cells. We previously reported that hypoxic conditions promote the internalization of vascular endothelial (VE)-cadherin, a specific cell-cell adhesion molecule, and increase the velocity of the collective migration of vascular endothelial cells. However, the mechanism through which cells regulate collective migration as affected by oxygen tension is not fully understood. Here, we investigated oxygen-dependent collective migration, focusing on intracellular protein p21-activated kinase (PAK) and hypoxia-inducing factor (HIF)-1α. A monolayer of human umbilical vein vascular endothelial cells (HUVECs) was formed in a microfluidic device with controllability of oxygen tension. The HUVECs were then exposed to various oxygen conditions in a range from 0.8% to 21% O<sub>2</sub>, with or without PAK inhibition or chemical stabilization of HIF-1α. Collective cell migration was measured by particle image velocimetry with time-lapse phase-contrast microscopic images. Localizations of VE-cadherin and HIF-1α were quantified by immunofluorescent staining. The collective migration of HUVECs varied in an oxygen-dependent fashion; the migration speed was increased by hypoxic exposure down to 1% O<sub>2</sub>, while it decreased under an extremely low oxygen tension of less than 1% O<sub>2</sub>. PAK inhibition suppressed the hypoxia-induced increase of the migration speed by preventing VE-cadherin internalization into HUVECs. A decrease in the migration speed was also obtained by chemical stabilization of HIF-1α, suggesting that excessive accumulation of HIF-1α diminishes collective cell migration. These results indicate that the oxygen-dependent variation of the migration speed of vascular endothelial cells is mediated by the regulation of VE-cadherin through the PAK pathway, as well as other mechanisms via HIF-1α, especially under extreme hypoxic conditions.</p>","PeriodicalId":9680,"journal":{"name":"Cell Adhesion & Migration","volume":"15 1","pages":"272-284"},"PeriodicalIF":3.2,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39437794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Catherine J Libby, Sajina Gc, Gloria A Benavides, Jennifer L Fisher, Sarah E Williford, Sixue Zhang, Anh Nhat Tran, Emily R Gordon, Amber B Jones, Kaysaw Tuy, William Flavahan, Juan Gordillo, Ashlee Long, Sara J Cooper, Brittany N Lasseigne, Corinne E Augelli-Szafran, Victor Darley-Usmar, Anita B Hjelmeland
{"title":"A role for GLUT3 in glioblastoma cell invasion that is not recapitulated by GLUT1.","authors":"Catherine J Libby, Sajina Gc, Gloria A Benavides, Jennifer L Fisher, Sarah E Williford, Sixue Zhang, Anh Nhat Tran, Emily R Gordon, Amber B Jones, Kaysaw Tuy, William Flavahan, Juan Gordillo, Ashlee Long, Sara J Cooper, Brittany N Lasseigne, Corinne E Augelli-Szafran, Victor Darley-Usmar, Anita B Hjelmeland","doi":"10.1080/19336918.2021.1903684","DOIUrl":"https://doi.org/10.1080/19336918.2021.1903684","url":null,"abstract":"<p><p>The multifaceted roles of metabolism in invasion have been investigated across many cancers. The brain tumor glioblastoma (GBM) is a highly invasive and metabolically plastic tumor with an inevitable recurrence. The neuronal glucose transporter 3 (GLUT3) was previously reported to correlate with poor glioma patient survival and be upregulated in GBM cells to promote therapeutic resistance and survival under restricted glucose conditions. It has been suggested that the increased glucose uptake mediated by GLUT3 elevation promotes survival of circulating tumor cells to facilitate metastasis. Here we suggest a more direct role for GLUT3 in promoting invasion that is not dependent upon changes in cell survival or metabolism. Analysis of glioma datasets demonstrated that GLUT3, but not GLUT1, expression was elevated in invasive disease. In human xenograft derived GBM cells, GLUT3, but not GLUT1, elevation significantly increased invasion in transwell assays, but not growth or migration. Further, there were no changes in glycolytic metabolism that correlated with invasive phenotypes. We identified the GLUT3 C-terminus as mediating invasion: substituting the C-terminus of GLUT1 for that of GLUT3 reduced invasion. RNA-seq analysis indicated changes in extracellular matrix organization in GLUT3 overexpressing cells, including upregulation of osteopontin. Together, our data suggest a role for GLUT3 in increasing tumor cell invasion that is not recapitulated by GLUT1, is separate from its role in metabolism and survival as a glucose transporter, and is likely broadly applicable since GLUT3 expression correlates with metastasis in many solid tumors.</p>","PeriodicalId":9680,"journal":{"name":"Cell Adhesion & Migration","volume":"15 1","pages":"101-115"},"PeriodicalIF":3.2,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336918.2021.1903684","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25580921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Deborah J Wessels, Claude Pujol, Nikash Pradhan, Daniel F Lusche, Luis Gonzalez, Sydney E Kelly, Elizabeth M Martin, Edward R Voss, Yang-Nim Park, Michael Dailey, Sonia L Sugg, Sneha Phadke, Amani Bashir, David R Soll
{"title":"Directed movement toward, translocation along, penetration into and exit from vascular networks by breast cancer cells in 3D.","authors":"Deborah J Wessels, Claude Pujol, Nikash Pradhan, Daniel F Lusche, Luis Gonzalez, Sydney E Kelly, Elizabeth M Martin, Edward R Voss, Yang-Nim Park, Michael Dailey, Sonia L Sugg, Sneha Phadke, Amani Bashir, David R Soll","doi":"10.1080/19336918.2021.1957527","DOIUrl":"https://doi.org/10.1080/19336918.2021.1957527","url":null,"abstract":"<p><p>We developed a computer-assisted platform using laser scanning confocal microscopy to 3D reconstruct in real-time interactions between metastatic breast cancer cells and human umbilical vein endothelial cells (HUVECs). We demonstrate that MB-231 cancer cells migrate toward HUVEC networks, facilitated by filopodia, migrate along the network surfaces, penetrate into and migrate within the HUVEC networks, exit and continue migrating along network surfaces. The system is highly amenable to 3D reconstruction and computational analyses, and assessments of the effects of potential anti-metastasis monoclonal antibodies and other drugs. We demonstrate that an anti-RHAMM antibody blocks filopodium formation and all of the behaviors that we found take place between MB-231 cells and HUVEC networks.</p>","PeriodicalId":9680,"journal":{"name":"Cell Adhesion & Migration","volume":"15 1","pages":"224-248"},"PeriodicalIF":3.2,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336918.2021.1957527","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39267512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanling Jin, Wei Liu, Fengxia Wang, Min Wang, Kai Xu, Aijun Yang, Chenyu Wang, Lihan Zhang, Fangfang Zhang, Min Li
{"title":"Tissue factor potentiates adherence of breast cancer cells to human umbilical vein endothelial cells under static and flow conditions.","authors":"Yanling Jin, Wei Liu, Fengxia Wang, Min Wang, Kai Xu, Aijun Yang, Chenyu Wang, Lihan Zhang, Fangfang Zhang, Min Li","doi":"10.1080/19336918.2021.1898709","DOIUrl":"https://doi.org/10.1080/19336918.2021.1898709","url":null,"abstract":"<p><p>Tissue factor (TF) has been extensively studied for tumor metastasis, but its role in mediating cancer cell adhesion to vasculature remains unknown. This study aimed to measure the ability of TF to mediate the adhesion of breast cancer cells to human umbilical vein endothelial cells (HUVECs). MDA-MB-231 cells expressed the highest TF level and adhered more to HUVECs under static and flow conditions, a neutralizing TF antibody abolished the enhanced adhesion of MDA-MB-231 cells to HUVECs. Recombinant human soluble TF (rTF) bonded β1integrin on HUVECs surfaces, β1 or α3integrin antibody combined with TF antibody abolished more cell-cell adhesion. These data suggested that TF mediated adhesion of breast cancer cells to endothelial cells may rely on β1integrin on HUVECs surfaces.</p>","PeriodicalId":9680,"journal":{"name":"Cell Adhesion & Migration","volume":"15 1","pages":"74-83"},"PeriodicalIF":3.2,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336918.2021.1898709","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25500666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Begoña Alday-Parejo, Kedar Ghimire, Oriana Coquoz, Gioele W Albisetti, Luca Tamò, Jelena Zaric, Jimmy Stalin, Curzio Rüegg
{"title":"MAGI1 localizes to mature focal adhesion and modulates endothelial cell adhesion, migration and angiogenesis.","authors":"Begoña Alday-Parejo, Kedar Ghimire, Oriana Coquoz, Gioele W Albisetti, Luca Tamò, Jelena Zaric, Jimmy Stalin, Curzio Rüegg","doi":"10.1080/19336918.2021.1911472","DOIUrl":"https://doi.org/10.1080/19336918.2021.1911472","url":null,"abstract":"<p><p>MAGI1 is an intracellular adaptor protein that stabilizes cell junctions and regulates epithelial and endothelial integrity. Here, we report that that in endothelial cells MAGI1 colocalizes with paxillin, β3-integrin, talin 1, tensin 3 and α-4-actinin at mature focal adhesions and actin stress fibers, and regulates their dynamics. Downregulation of MAGI1 reduces focal adhesion formation and maturation, cell spreading, actin stress fiber formation and RhoA/Rac1 activation. MAGI1 silencing increases phosphorylation of paxillin at Y118, an indicator of focal adhesion turnover. MAGI1 promotes integrin-dependent endothelial cells adhesion to ECM, reduces invasion and tubulogenesis<i>in vitro</i> and suppresses angiogenesis <i>in vivo</i>. Our results identify MAGI1 as anovel component of focal adhesions, and regulator of focal adhesion dynamics, cell adhesion, invasion and angiogenesis.</p>","PeriodicalId":9680,"journal":{"name":"Cell Adhesion & Migration","volume":"15 1","pages":"126-139"},"PeriodicalIF":3.2,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336918.2021.1911472","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25565481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nicotinate-curcumin inhibits AngII-induced vascular smooth muscle cell phenotype switching by upregulating Daxx expression.","authors":"Si-Yu Sun, Yu-Mei Cao, Yan-Jie Huo, Fei Qiu, Wen-Juan Quan, Chao-Ping He, Yu Chen, Duan-Fang Liao, Qin-Hui Tuo","doi":"10.1080/19336918.2021.1909899","DOIUrl":"https://doi.org/10.1080/19336918.2021.1909899","url":null,"abstract":"<p><p>Phenotypic switching is the main cause of the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs). We previously showed that Daxx exerted negative regulatory effect on AngII-induced VSMC proliferation and migration. However, the function of Daxx in VSMC phenotype switching remained unknown. Nicotinate-curcumin (NC) is an esterification derivative of niacin and curcumin that can prevent the formation of atherosclerosis. We found that NC significantly decreased AngII-induced VSMC phenotype switching. Furthermore, NC significantly inhibited AngII-induced cell proliferation and migration. Moreover, NC upregulated Daxx expression and regulated the PTEN/Akt signaling pathway. We concluded that NC inhibited AngII-induced VSMC phenotype switching by regulating the PTEN/Akt pathway, and through a mechanism that might be associated with the upregulation of Daxx expression.</p>","PeriodicalId":9680,"journal":{"name":"Cell Adhesion & Migration","volume":"15 1","pages":"116-125"},"PeriodicalIF":3.2,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336918.2021.1909899","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25599352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francesco Roncato, Ofer Regev, Sandeep Kumar Yadav, Ronen Alon
{"title":"Microtubule destabilization is a critical checkpoint of chemotaxis and transendothelial migration in melanoma cells but not in T cells.","authors":"Francesco Roncato, Ofer Regev, Sandeep Kumar Yadav, Ronen Alon","doi":"10.1080/19336918.2021.1934958","DOIUrl":"https://doi.org/10.1080/19336918.2021.1934958","url":null,"abstract":"<p><p>Microtubules (MTs) control cell shape and intracellular cargo transport. The role of MT turnover in the migration of slow-moving cells through endothelial barriers remains unclear. To irreversibly interfere with MT disassembly, we have used the MT-stabilizing agent zampanolide (ZMP) in Β16F10 melanoma as amodel of slow-moving cells. ZMP-treated B16 cells failed to follow chemotactic gradients across rigid confinements and could not generate stable sub-endothelial pseudopodia under endothelial monolayers. In vivo, ZMP-treated Β16 cells failed to extravasate though lung capillaries. In contrast to melanoma cells, the chemotaxis and transendothelial migration of ZMP-treated Tcells were largely conserved. This is afirst demonstration that MT disassembly is akey checkpoint in the directional migration of cancer cells but not of lymphocytes.</p>","PeriodicalId":9680,"journal":{"name":"Cell Adhesion & Migration","volume":"15 1","pages":"166-179"},"PeriodicalIF":3.2,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336918.2021.1934958","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39252968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kateřina Kuželová, Adam Obr, Pavla Röselová, Dana Grebeňová, Petra Otevřelová, Barbora Brodská, Aleš Holoubek
{"title":"Group I p21-activated kinases in leukemia cell adhesion to fibronectin.","authors":"Kateřina Kuželová, Adam Obr, Pavla Röselová, Dana Grebeňová, Petra Otevřelová, Barbora Brodská, Aleš Holoubek","doi":"10.1080/19336918.2021.1872760","DOIUrl":"https://doi.org/10.1080/19336918.2021.1872760","url":null,"abstract":"<p><p>P21-activated kinases (PAK) regulate processes associated with cytoskeleton dynamics. PAK expression in leukemia cells was measured on protein and mRNA levels. In functional assays, we analyzed the effect of PAK inhibitors IPA-3 and FRAX597 on cell adhesivity and viability. PAK2 was dominant in cell lines, whereas primary cells also expressed comparable amount of PAK1 transcription isoforms: PAK1-full and PAK1Δ15. PAK1Δ15 and PAK2 levels correlated with surface density of integrins β1 and αVβ3. PAK1-full, but not PAK2, was present in membrane protrusions. IPA-3, which prevents PAK activation, induced cell contraction in semi-adherent HEL cells only. FRAX597, which inhibits PAK kinase activity, increased cell-surface contact area in all leukemia cells. Both inhibitors reduced the stability of cell attachment and induced cell death.</p>","PeriodicalId":9680,"journal":{"name":"Cell Adhesion & Migration","volume":"15 1","pages":"18-36"},"PeriodicalIF":3.2,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336918.2021.1872760","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38768449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}