scholarly journals Adhesion and Stiffness of Detached Breast Cancer Cells In Vitro: Co-Treatment with Metformin and 2-Deoxy-d-glucose Induces Changes Related to Increased Metastatic Potential

Biology ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 873
Author(s):  
Špela Zemljič-Jokhadar ◽  
Gašper Kokot ◽  
Mojca Pavlin ◽  
Jure Derganc

Metastatic cancer cells can overcome detachment-induced cell death and can proliferate in anchorage-independent conditions. A recent study revealed that a co-treatment with two drugs that interfere with cell metabolism, metformin and 2-deoxy-D-glucose, promotes detachment of viable MDA-MB-231 breast cancer cells. In the present study, we analyzed if these detached viable MDA-MB-231 cells also exhibit other features related to cancer metastatic potential, i.e., if they are softer and more prone to adhere to epithelial cells. The cell mechanics of attached cells and floating cells were analyzed by optical tweezers and cell deformability cytometry, respectively. The adhesion was assessed on a confluent monolayer of HUVEC cells, with MDA-MB-231 cells either in static conditions or in a microfluidic flow. Additionally, to test if adhesion was affected by the state of the epithelial glycocalyx, HUVEC cells were treated with neuraminidase and tunicamycin. It was found that the treated MDA-MB-231 cells were more prone to adhere to HUVEC cells and that they were softer than the control, both in the floating state and after re-seeding to a substrate. The changes in the HUVEC glycocalyx, however, did not increase the adhesion potential of MDA-MB-231.

2021 ◽  
Author(s):  
Deborah Fanfone ◽  
Zhi Chong Wu ◽  
Jade Mammi ◽  
Kevin Berthenet ◽  
David Neves ◽  
...  

Mechanical stress is known to fuel several hallmarks of cancer, ranging from genome instability to uncontrolled proliferation or invasion. Cancer cells are constantly challenged by mechanical stresses not only in the primary tumour but also during metastasis. However, this latter has seldom been studied with regards to mechanobiology, in particular resistance to anoikis, a cell death programme triggered by loss of cell adhesion. Here, we show in vitro that migrating breast cancer cells develop resistance to anoikis following their passage through microporous membranes mimicking confined migration (CM), a mechanical constriction that cancer cells encounter during metastasis. This CM-induced resistance was mediated by Inhibitory of Apoptosis Proteins (IAPs), and sensitivity to anoikis could be restored after their inhibition using SMAC mimetics. Anoikis-resistant mechanically-stressed cancer cells displayed enhanced cell motility and evasion from natural killer cell-mediated immune surveillance, as well as a marked advantage to form lung metastatic lesions in mice. Our findings reveal that CM increases the metastatic potential of breast cancer cells.


2018 ◽  
Vol 120 (5) ◽  
pp. 7590-7601 ◽  
Author(s):  
Yu‐Heng Vivian Ma ◽  
Liangcheng Xu ◽  
Xueting Mei ◽  
Kevin Middleton ◽  
Lidan You

2019 ◽  
Vol 19 (22) ◽  
pp. 2069-2078 ◽  
Author(s):  
Leonel Montealegre-Sánchez ◽  
Sarah N.C. Gimenes ◽  
Daiana S. Lopes ◽  
Samuel C. Teixeira ◽  
Luis Solano-Redondo ◽  
...  

Background: Disintegrins from snake venoms bind with high specificity cell surface integrins, which are important pharmacological targets associated with cancer development and progression. Objective: In this study, we isolated a disintegrin from the Porthidium lansbergii lansbergii venom and evaluated its antitumoral effects on breast cancer cells. Methods: The isolation of the disintegrin was performed on RP-HPLC and the inhibition of platelet aggregation was evaluated on human platelet-rich plasma. The inhibition of cell adhesion was also evaluated in vitro on cultures of cell lines by the MTT method as well as the inhibition of breast cancer cell migration by the wound healing assay. The binding of the disintegrin to integrin subunits was verified by flow cytometry and confocal microscopy. Finally, inhibition of angiogenesis was assessed in vitro on HUVEC cells and the concentration of VEGF was measured in the cellular supernatants. Results: The disintegrin, named Lansbermin-I, is a low molecular weight protein (< 10 kDa) that includes an RGD on its sequence identified previously. Lansbermin-I showed potent inhibition of ADP and collagen-induced platelet aggregation on human plasma and also displayed inhibitory effects on the adhesion and migration of breast cancer MCF7 and MDA-MB 231cell lines, without affecting nontumorigenic breast MCF-10A and lung BEAS cells. Additionally, Lansbermin-I prevented MCF7 cells to adhere to fibronectin and collagen, and also inhibited in vitro angiogenesis on human endothelial HUVEC cells. Conclusion: Our results display the first report on the antitumor and anti-metastatic effects of an RGDdisintegrin isolated from a Porthidium snake venom by possibly interfering with α2 and/or β1-containing integrins. Thus, Lansbermin-I could be an attractive model to elucidate the role of disintegrins against breast cancer development.


2015 ◽  
Vol 7 (24) ◽  
pp. 10162-10169 ◽  
Author(s):  
Qifei Li ◽  
Lifu Xiao ◽  
Sitaram Harihar ◽  
Danny R. Welch ◽  
Elizabeth Vargis ◽  
...  

Breast cancer cells with or without BRMS1 in response to doxorubicin (DOX).


2020 ◽  
Vol 6 (2) ◽  
Author(s):  
Lisni Noraida Waruwu ◽  
Maria Bintang ◽  
Bambang Pontjo Priosoeryanto

Green tea (Camellia sinensis) is one of traditional plants that have the potential as an anticancer. The sample used in this research commercial green tea extract. The purpose of this study was to test the antiproliferation activity of green tea extract on breast cancer cell MCM-B2 in vitro. Green tea extract fractionated using three solvents, ie water, ethanol 70%, and n-hexane. Extract and fraction of green tea water have value Lethality Concentration 50 (LC50) more than 1000 ppm. The fraction of ethanol 70% and n-hexane had an LC50 value of 883.48 ppm and 600.56 ppm, respectively. The results of the phytochemical screening of green tea extract are flavonoids, tannins, and saponins, while the phytochemical screening results of n-hexane fraction are flavonoids and tannins. Antiproliferation activity was tested on breast cancer cells MCM-B2 and normal cells Vero by trypan blue staining method. The highest MCM-B2 cell inhibitory activity was achieved at a concentration of 13000 ppm green tea extract and 1000 ppm of n-hexane fraction, 59% and 59%, respectively. The extract and n-hexane fraction of green tea are not toxic to normal Vero cells characterized by not inhibiting normal cell proliferation. Keywords: antiproliferative, cancer cell MCM-B2, commercial green tea, cytotoxicity


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