An in vitro study on the collective tumor cell migration on nanoroughened poly(dimethylsiloxane) surfaces

2015 ◽  
Vol 3 (8) ◽  
pp. 1565-1572 ◽  
Author(s):  
Jingjing Han ◽  
Nishanth V. Menon ◽  
Yuejun Kang ◽  
Shang-You Tee

A simple and effective method to engineer surface nanoroughness contrast for a comparative study on the collective migration of tumor cells.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23149-e23149
Author(s):  
Thomas Nelius ◽  
Courtney Jarvis ◽  
Stephanie Filleur

e23149 Background: Despite the approval of several new agents, taxanes remains the main treatment with survival benefits for castration-refractory metastatic prostate cancer/mCRPC. Still their mechanisms of action and therapeutic efficacy remain incompletely characterized. In the present study, we proposed to compare docetaxel/Doc and cabazitaxel/Cab, delivered as monotherapy or in combination with the anti-angiogenic and anti-tumoral Pigment Epithelium-Derived Factor/PEDF, on CRPC cells in vitro and in vivo. Methods: CRPCcells were assessed for cell growth, cell cycle, and apoptosis under taxane/control treatment by cytotoxicity, PI incorporation and TUNEL assays. CL1 cells that express PEDF/control were used in vivo. Tumor cells were injected s.c. into CB17-SCID mice. After two weeks, mice were randomized into groups: 1) Placebo; 2) Doc 5mg/kg i.p. d4; and 3) Cab 5-1-0.5-0.1mg/kg i.p. d4, d1-7, d2, daily. To assess the anti-tumor effect of the combination, tumor cell migration and phagocytosis were measured by Boyden chamber and confocal microscopy analyses of CL1-RAW264.7 macrophages co-cultures. Results: Cab was more cytotoxic than Doc in all the cell lines tested.This effect was concomitant to increased cell death, but was not due to autophagy or necrosis. Inversely, we showed that apoptosis was superior in Cab-treated cells than in Doc treatment. In vivo, while 0.5 and 0.1 mg/kg Cab did not improve PEDF efficacy on tumor growth, 1mg/kg was very toxic. In contrast, PEDF combined with 5mg/kg Cab lead to stabilization of the disease and was also found to be drastically more efficient than PEDF/Doc in delaying the disease. In vitro, PEDF/Cab inhibited tumor cell migration at a significant superior level compared to PEDF/Doc. Finally, tumor cells phagocytosis was induced in PEDF/Cab suggesting that the combination may target macrophages within the tumor microenvironment. Conclusions: Our data demonstrated the greater anti-tumor efficacy of Cab compared to Doc. They also insist on the fact that PEDF/Cab could be used as a novel combined therapy for CRPC, and emphasize on the importance in evaluating the cytotoxicity of the novel combination tested and investigating the role of the tumor microenvironment in the anti-tumor effect.


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 275-275
Author(s):  
Thomas Nelius ◽  
Courtney Jarvis ◽  
Stephanie Filleur

275 Background: Despite the approval of several new agents, taxanes remain the main alternative treatment for castration-refractory metastatic prostate cancer (mCRPC). In a previous work, we have demonstrated that cabazitaxel is more efficient in a low-dose setting than docetaxel in inhibiting the proliferation and inducing apoptosis of CRPC cells in vitro, and delaying tumor growth in vivo. In the present study, we have investigated the efficacy of low-dose cabazitaxel when combined with the anti-angiogenic and anti-tumoral Pigment Epithelium-Derived Factor (PEDF). Methods: CRPC CL1 cells (LNCaP-derivative) that express PEDF or control plasmid were used. Tumor cells were injected s.c. into C.B.17-SCID mice. After two weeks, mice were randomized into groups: 1) Placebo; 2) Docetaxel: 5mg/kg i.p. d4; and 3) Cabazitazel 5-1-0.5-0.1mg/kg i.p. d4, d1-7, d2, and daily. To investigate the molecular mechanisms involved in the anti-tumor effect of the combined treatment, tumor cell migration was measured using the inverted Boyden chamber assay. Tumor cell phagocytosis was also assessed in CL1-RAW264.7 macrophages co-cultures. Results: We showed that while 0.5 and 0.1 mg/kg cabazitaxel did not improve PEDF efficacy on tumor growth, 1mg/kg was extremely toxic, killing 1/2 animals within the first week of treatment. In contrast, we demonstrated that PEDF combined with 5mg/kg cabazitaxel lead to stabilization of the disease. PEDF/cabazitaxel was also found to be drastically more efficient than PEDF/docetaxel in delaying the disease. In vitro, PEDF/cabazitaxel inhibited tumor cell migration at a superior level compared to PEDF/docetaxel. Finally, PEDF/cabazitaxel induced more phagocytosis of the tumor cells by macrophages than PEDF/docetaxel suggesting that the combination may target macrophages within the tumor microenvironment. Conclusions: Our data demonstrated that PEDF with low-dose cabazitaxel could be used as a novel therapeutic combination to treat CRPC. Our results also emphasize on the importance in closely evaluating the cytotoxicity of the combination tested and investigating the role of the tumor microenvironment in the anti-tumor effect.


2003 ◽  
Vol 160 (2) ◽  
pp. 267-277 ◽  
Author(s):  
Katarina Wolf ◽  
Irina Mazo ◽  
Harry Leung ◽  
Katharina Engelke ◽  
Ulrich H. von Andrian ◽  
...  

Invasive tumor dissemination in vitro and in vivo involves the proteolytic degradation of ECM barriers. This process, however, is only incompletely attenuated by protease inhibitor–based treatment, suggesting the existence of migratory compensation strategies. In three-dimensional collagen matrices, spindle-shaped proteolytically potent HT-1080 fibrosarcoma and MDA-MB-231 carcinoma cells exhibited a constitutive mesenchymal-type movement including the coclustering of β1 integrins and MT1–matrix metalloproteinase (MMP) at fiber bindings sites and the generation of tube-like proteolytic degradation tracks. Near-total inhibition of MMPs, serine proteases, cathepsins, and other proteases, however, induced a conversion toward spherical morphology at near undiminished migration rates. Sustained protease-independent migration resulted from a flexible amoeba-like shape change, i.e., propulsive squeezing through preexisting matrix gaps and formation of constriction rings in the absence of matrix degradation, concomitant loss of clustered β1 integrins and MT1-MMP from fiber binding sites, and a diffuse cortical distribution of the actin cytoskeleton. Acquisition of protease-independent amoeboid dissemination was confirmed for HT-1080 cells injected into the mouse dermis monitored by intravital multiphoton microscopy. In conclusion, the transition from proteolytic mesenchymal toward nonproteolytic amoeboid movement highlights a supramolecular plasticity mechanism in cell migration and further represents a putative escape mechanism in tumor cell dissemination after abrogation of pericellular proteolysis.


2021 ◽  
Vol 18 (2) ◽  
pp. 38
Author(s):  
SamarH Makled ◽  
FadelA Abd Elfatah ◽  
MohamedN El-Guindy

2021 ◽  
Vol 13 (02) ◽  
pp. 55-61
Author(s):  
Revathi Bashyam ◽  
Ramesh Krishnan ◽  
Kruthika Murali ◽  
Nandhini B. Selvarajan ◽  
Suresh Kumar Vasaviah ◽  
...  

2019 ◽  
Vol 11 (7) ◽  
pp. 515 ◽  
Author(s):  
KrantiKiran Reddy Ealla ◽  
AshokBabu Devatha ◽  
MNarasimha Lakshmi ◽  
NareshB Kumar ◽  
Srikanth Erukala ◽  
...  

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