scholarly journals Stem-like Cancer Cells in a Dynamic 3D Culture System: A Model to Study Metastatic Cell Adhesion and Anti-cancer Drugs

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1434 ◽  
Author(s):  
Paolillo ◽  
Colombo ◽  
Serra ◽  
Belvisi ◽  
Papetti ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cancer Cells ◽  
Culture System ◽  
Human Fibroblasts ◽  
3D Culture ◽  
Target Tissue ◽  
Cancer Drugs ◽  
Mesenchymal Transition ◽  
Anti Cancer

Metastatic spread is mainly sustained by cancer stem cells (CSC), a subpopulation of cancer cells that displays stemness features. CSC are thought to be derived from cancer cells that undergo epithelial to mesenchymal transition (EMT), thus acquiring resistance to anoikis and anti-cancer drugs. After detachment from the primary tumor mass, CSC reach the blood and lymphatic flow, and disseminate to the target tissue. This process is by nature dynamic and in vitro models are quite far from the in vivo situation. In this study, we have tried to reproduce the adhesion process of CSC to a target tissue by using a 3D dynamic cell culture system. We isolated two populations of 3D tumor spheroids displaying CSC-like features from breast carcinoma (MCF-7) and lung carcinoma (A549) cell lines. Human fibroblasts were layered on a polystyrene scaffold placed in a dynamically perfused millifluidic system and then the adhesion of tumor cell derived from spheroids to fibroblasts was investigated under continuous perfusion. After 24 h of perfusion, we found that spheroid cells tightly adhered to fibroblasts layered on the scaffold, as assessed by a scanning electron microscope (SEM). To further investigate mechanisms involved in spheroid cell adhesion to fibroblasts, we tested the effect of three RGD integrin antagonists with different molecular structures on cell adhesion; when injected into the circuit, only cilengitide was able to inhibit cell adhesion to fibroblasts. Although our model needs further refinements and improvements, we do believe this study could represent a promising approach in improving current models to study metastatic infiltration in vitro and a new tool to screen new potential anti-metastatic molecules.

scholarly journals Three-Dimensional Culture System of Cancer Cells Combined with Biomaterials for Drug Screening

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2754 ◽  
Author(s):  
Teruki Nii ◽  
Kimiko Makino ◽  
Yasuhiko Tabata
Keyword(s):  
Cell Culture ◽  
Cancer Cells ◽  
Drug Screening ◽  
Culture System ◽  
Three Dimensional ◽  
3D Culture ◽  
New Drugs ◽  
Biological Research

Anticancer drug screening is one of the most important research and development processes to develop new drugs for cancer treatment. However, there is a problem resulting in gaps between the in vitro drug screening and preclinical or clinical study. This is mainly because the condition of cancer cell culture is quite different from that in vivo. As a trial to mimic the in vivo cancer environment, there has been some research on a three-dimensional (3D) culture system by making use of biomaterials. The 3D culture technologies enable us to give cancer cells an in vitro environment close to the in vivo condition. Cancer cells modified to replicate the in vivo cancer environment will promote the biological research or drug discovery of cancers. This review introduces the in vitro research of 3D cell culture systems with biomaterials in addition to a brief summary of the cancer environment.

Molecular Targets, Anti-cancer Properties and Potency of Synthetic Indole-3-carbinol Derivatives

2019 ◽  
Vol 19 (7) ◽  
pp. 540-554 ◽  
Author(s):  
Mojgan Noroozi Karimabad ◽  
Mehdi Mahmoodi ◽  
Abdolah Jafarzadeh ◽  
Ali Darekordi ◽  
Mohamad Reza Hajizadeh ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Cellular Proliferation ◽  
Human Cancer ◽  
Molecular Targets ◽  
Tumor Formation ◽  
Mesenchymal Transition ◽  
Anti Cancer

The indole-3-carbinol (I3C) displays anti-cancer/proliferative activities against human cancer cells. Cellular proliferation is an event associated with the progress and its continuation. This manifest is described by variation in expression and/or functions of genes that are related with cell cycle relevant proteins. The constitutive activation of several signal transduction pathways stimulates cells proliferation as well. The immediate stages in cancer development are accompanied by a fibrogenic response and the progression of the hypoxic environment is in favor of survival and proliferatory functions of cancer stem cells. A main part for prevention of in cancer cells death may manifest through altering cell metabolism. Cellular proliferation and metastasis are reported to be supported with increased generation of responsible hormones (in hormone dependent malignancies), and further promotion the angiogenesis, with epithelial to mesenchymal transition. This may be facilitated by progression of autophagy phenomenon, as well as via taking cues from neighboring stromal cells. Several signaling pathways in association with various factors specific for cellular viability, including hypoxia inducible factor 1, NF-κB, insulin-like growth factor 1 (IGF-1) receptor, Human foreskin fibroblasts (HFF-1), phosphoinositide 3 kinase/Akt, Wnt, cell cycle related protein, with androgen and estrogen receptor signaling are reported to be inhibited by I3C. These evidences, in association with bioinformatics data represent very important information for describing signaling pathways in parallel with molecular targets that may serve as markers for early diagnosis and/or critical targets for designing and development of novel therapeutic regimes alone or combined with drugs, to prevent tumor formation and further progression. In particular, I3C and DIM have been extensively investigated for their importance against numbers human cancers both in vitro and in vivo. We aimed the present manuscript, current study, to review anticancer properties and the miscellaneous mechanisms underlying the antitumorigenicity in an in-depth study for broadening the I3C treating marvel.

scholarly journals Differences in the Central Energy Metabolism of Cancer Cells between Conventional 2D and Novel 3D Culture Systems

2021 ◽  
Vol 22 (4) ◽  
pp. 1805
Author(s):  
Ryo Ikari ◽  
Ken-ichi Mukaisho ◽  
Susumu Kageyama ◽  
Masayuki Nagasawa ◽  
Shigehisa Kubota ◽  
...  
Keyword(s):  
Cell Culture ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Culture System ◽  
3D Culture ◽  
Cell Culture System ◽  
Metabolome Analysis ◽  
Wide Range

The conventional two-dimensional (2D) culture is available as an in vitro experimental model. However, the culture system reportedly does not recapitulate the in vivo cancer microenvironment. We recently developed a tissueoid cell culture system using Cellbed, which resembles the loose connective tissue in living organisms. The present study performed 2D and three-dimensional (3D) culture using prostate and bladder cancer cell lines and a comprehensive metabolome analysis. Compared to 3D, the 2D culture had significantly lower levels of most metabolites. The 3D culture system did not impair mitochondrial function in the cancer cells and produce energy through the mitochondria simultaneously with aerobic glycolysis. Conversely, ATP production, biomass (nucleotides, amino acids, lipids and NADPH) synthesis and redox balance maintenance were conducted in 3D culture. In contrast, in 2D culture, biomass production was delayed due to the suppression of metabolic activity. The 3D metabolome analysis using the tissueoid cell culture system capable of in vivo cancer cell culture yielded results consistent with previously reported cancer metabolism theories. This system is expected to be an essential experimental tool in a wide range of cancer research fields, especially in preclinical stages while transitioning from in vitro to in vivo.

Chalcone-Coumarin Derivatives as Potential Anti-Cancer Drugs: An in vitro and in vivo Investigation

2013 ◽  
Vol 14 (7) ◽  
pp. 963-974 ◽  
Author(s):  
Vincent Jamier ◽  
Wioleta Marut ◽  
Sergio Valente ◽  
Christiane Chereau ◽  
Sandrine Chouzenoux ◽  
...  
Keyword(s):  
Coumarin Derivatives ◽  
Cancer Drugs ◽  
Anti Cancer

scholarly journals CXCL2-CXCR2 axis mediates αV integrin-dependent peritoneal metastasis of colon cancer cells

2021 ◽  
Author(s):  
Mattias Lepsenyi ◽  
Nader Algethami ◽  
Amr A. Al-Haidari ◽  
Anwar Algaber ◽  
Ingvar Syk ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Adhesion ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Colon Cancer Cell ◽  
Colon Cancer Cells ◽  
Cancer Cell Adhesion ◽  
And Migration ◽  
Cxcr2 Antagonist

AbstractPeritoneal metastasis is an insidious aspect of colorectal cancer. The aim of the present study was to define mechanisms regulating colon cancer cell adhesion and spread to peritoneal wounds after abdominal surgery. Mice was laparotomized and injected intraperitoneally with CT-26 colon carcinoma cells and metastatic noduli in the peritoneal cavity was quantified after treatment with a CXCR2 antagonist or integrin-αV-antibody. CT-26 cells expressed cell surface chemokine receptors CXCR2, CXCR3, CXCR4 and CXCR5. Stimulation with the CXCR2 ligand, CXCL2, dose-dependently increased proliferation and migration of CT-26 cells in vitro. The CXCR2 antagonist, SB225002, dose-dependently decreased CXCL2-induced proliferation and migration of colon cancer cells in vitro. Intraperitoneal administration of CT-26 colon cancer cells resulted in wide-spread growth of metastatic nodules at the peritoneal surface of laparotomized animals. Laparotomy increased gene expression of CXCL2 at the incisional line. Pretreatment with CXCR2 antagonist reduced metastatic nodules by 70%. Moreover, stimulation with CXCL2 increased CT-26 cell adhesion to extracellular matrix (ECM) proteins in a CXCR2-dependent manner. CT-26 cells expressed the αV, β1 and β3 integrin subunits and immunoneutralization of αV abolished CXCL2-triggered adhesion of CT-26 to vitronectin, fibronectin and fibrinogen. Finally, inhibition of the αV integrin significantly attenuated the number of carcinomatosis nodules by 69% in laparotomized mice. These results were validated by use of the human colon cancer cell line HT-29 in vitro. Our data show that colon cancer cell adhesion and growth on peritoneal wound sites is mediated by a CXCL2-CXCR2 signaling axis and αV integrin-dependent adhesion to ECM proteins.

scholarly journals Doxorubicin loaded magnetism nanoparticles based on cyclodextrin dendritic-graphene oxide inhibited MCF-7 cell proliferation

2021 ◽  
Vol 12 (1) ◽  
pp. 8-15
Author(s):  
Ainaz Mihanfar ◽  
Niloufar Targhazeh ◽  
Shirin Sadighparvar ◽  
Saber Ghazizadeh Darband ◽  
Maryam Majidinia ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Anticancer Drug Delivery ◽  
Release Studies ◽  
Anti Cancer ◽  
Acidic Conditions ◽  
Mcf 7

Abstract Doxorubicin (DOX) is an effective chemotherapeutic agent used for the treatment of various types of cancer. However, its poor solubility, undesirable side effects, and short half-life have remained a challenge. We used a formulation based on graphene oxide as an anticancer drug delivery system for DOX in MCF-7 breast cancer cells, to address these issues. In vitro release studies confirmed that the synthesized formulation has an improved release profile in acidic conditions (similar to the tumor microenvironment). Further in vitro studies, including MTT, uptake, and apoptosis assays were performed. The toxic effects of the nanocarrier on the kidney, heart and liver of healthy rats were also evaluated. We observed that the DOX-loaded carrier improved the cytotoxic effect of DOX on the breast cell line compared to free DOX. In summary, our results introduce the DOX-loaded carrier as a potential platform for in vitro targeting of cancer cells and suggest further studies are necessary to investigate its in vivo anti-cancer potential.

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