Nanorobots Sense Local Physiochemical Heterogeneities of Tumor Matrisome

2020 ◽  
Author(s):  
Debayan Dasgupta ◽  
Dharma Pally ◽  
Deepak K. Saini ◽  
Ramray Bhat ◽  
Ambarish Ghosh
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Adhesive Force ◽  
Surrounding Tissue ◽  
Quantitative Measurements ◽  
Malignant Breast Tumor ◽  
Malignant Breast ◽  
Cancer Dissemination

The dissemination of cancer is brought about by continuous interaction of malignant cells with their surrounding tissue microenvironment. Understanding and quantifying the remodeling of local extracellular matrix (ECM) by invading cells can therefore provide fundamental insights into the dynamics of cancer dissemination. In this paper, we use an active and untethered nanomechanical tool, realized as magnetically driven nanorobots, to locally probe a 3D tissue culture microenvironment consisting of cancerous and non-cancerous epithelia, embedded within reconstituted basement membrane (rBM) matrix. Our assay is designed to mimic the in vivo histopathological milieu of a malignant breast tumor. We find that nanorobots preferentially adhere to the ECM near cancer cells: this is due to the distinct charge conditions of the cancer-remodeled ECM. Surprisingly, quantitative measurements estimate that the adhesive force increases with the metastatic ability of cancer cell lines, while the spatial extent of the remodeled ECM was measured to be approximately 40 μm for all cancer cell lines studied here. We hypothesized and experimentally confirmed that specific sialic acid linkages specific to cancer-secreted ECM may be a major contributing factor in determining this adhesive behavior. The findings reported here can lead to promising applications in cancer diagnosis, quantification of cancer aggression, in vivo drug delivery applications, and establishes the tremendous potential of magnetic nanorobots for fundamental studies of cancer biomechanics.

Nanorobots Sense Local Physiochemical Heterogeneities of Tumor Matrisome

2020 ◽  
Author(s):  
Debayan Dasgupta ◽  
Dharma Pally ◽  
Deepak K. Saini ◽  
Ramray Bhat ◽  
Ambarish Ghosh
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Adhesive Force ◽  
Surrounding Tissue ◽  
Quantitative Measurements ◽  
Malignant Breast Tumor ◽  
Malignant Breast ◽  
Cancer Dissemination

The dissemination of cancer is brought about by continuous interaction of malignant cells with their surrounding tissue microenvironment. Understanding and quantifying the remodeling of local extracellular matrix (ECM) by invading cells can therefore provide fundamental insights into the dynamics of cancer dissemination. In this paper, we use an active and untethered nanomechanical tool, realized as magnetically driven nanorobots, to locally probe a 3D tissue culture microenvironment consisting of cancerous and non-cancerous epithelia, embedded within reconstituted basement membrane (rBM) matrix. Our assay is designed to mimic the in vivo histopathological milieu of a malignant breast tumor. We find that nanorobots preferentially adhere to the ECM near cancer cells: this is due to the distinct charge conditions of the cancer-remodeled ECM. Surprisingly, quantitative measurements estimate that the adhesive force increases with the metastatic ability of cancer cell lines, while the spatial extent of the remodeled ECM was measured to be approximately 40 μm for all cancer cell lines studied here. We hypothesized and experimentally confirmed that specific sialic acid linkages specific to cancer-secreted ECM may be a major contributing factor in determining this adhesive behavior. The findings reported here can lead to promising applications in cancer diagnosis, quantification of cancer aggression, in vivo drug delivery applications, and establishes the tremendous potential of magnetic nanorobots for fundamental studies of cancer biomechanics.

scholarly journals Nanorobots as sensors for cancer microenvironment

2020 ◽  
Author(s):  
Debayan Dasgupta ◽  
Dharma Pally ◽  
Deepak Kumar Saini ◽  
Ramray Bhat ◽  
Ambarish Ghosh
Keyword(s):  
Sialic Acid ◽  
Cancer Cells ◽  
Adhesive Force ◽  
Quantitative Measurements ◽  
Magnetically Actuated ◽  
Malignant Breast Tumor ◽  
Malignant Breast ◽  
Quantitative Understanding ◽  
Cancerous Cells

Malignant cancer cells constantly interact with their surrounding environment and migrate by remodeling the local extracellular matrix (ECM). A quantitative understanding of the remodeled ECM can provide new insights into the process of metastasis. Cells suspended in 3D matrices can mimic many of the physicochemical and mechanical properties of tumors in vivo. Our system is designed to approximate the in vivo histopathological milieu of a malignant breast tumor. Nanorobots can be effective tools for studying cellular biophysics and probing the local rheology of biological systems. Here we demonstrate how magnetically actuated helical nanorobots can probe a 3D tissue co-culture consisting of both cancerous and non-cancerous cells. We find that nanorobots adhere preferentially near cancer cells due to the distinct charge conditions of the cancer-sculpted ECM. The spatial extent of the remodeled ECM was measured to be approximately 40 μm for all cells. However, quantitative measurements showed the adhesive force to increase with metastatic ability of the cell lines. We hypothesized and experimentally confirmed that specific sialic acid linkages related to cancer-secreted ECM may be a major contributing factor in determining this adhesive behavior. Cell-line specific anisotropy in sialic acid distribution was also discovered by nanorobots. These findings can lead to promising applications in cancer diagnosis and quantification of cancer aggression.

scholarly journals Design, Synthesis, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitory Activity

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1838
Author(s):  
Naglaa M. Ahmed ◽  
Mahmoud M. Youns ◽  
Moustafa K. Soltan ◽  
Ahmed M. Said
Keyword(s):  
Molecular Modeling ◽  
Antitumor Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Antitumor Agents ◽  
Cancer Cell Lines ◽  
Normal Cells

Scaffolds hybridization is a well-known drug design strategy for antitumor agents. Herein, series of novel indolyl-pyrimidine hybrids were synthesized and evaluated in vitro and in vivo for their antitumor activity. The in vitro antiproliferative activity of all compounds was obtained against MCF-7, HepG2, and HCT-116 cancer cell lines, as well as against WI38 normal cells using the resazurin assay. Compounds 1–4 showed broad spectrum cytotoxic activity against all these cancer cell lines compared to normal cells. Compound 4g showed potent antiproliferative activity against these cell lines (IC50 = 5.1, 5.02, and 6.6 μM, respectively) comparable to the standard treatment (5-FU and erlotinib). In addition, the most promising group of compounds was further evaluated for their in vivo antitumor efficacy against EAC tumor bearing mice. Notably, compound 4g showed the most potent in vivo antitumor activity. The most active compounds were evaluated for their EGFR inhibitory (range 53–79 %) activity. Compound 4g was found to be the most active compound against EGFR (IC50 = 0.25 µM) showing equipotency as the reference treatment (erlotinib). Molecular modeling study was performed on compound 4g revealed a proper binding of this compound inside the EGFR active site comparable to erlotinib. The data suggest that compound 4g could be used as a potential anticancer agent.

scholarly journals Tumorigenicity and Validity of Fluorescence Labelled Mesenchymal and Epithelial Human Oral Cancer Cell Lines in Nude Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Wei Xin Cai ◽  
Li Wu Zheng ◽  
Li Ma ◽  
Hong Zhang Huang ◽  
Ru Qing Yu ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Nude Mice ◽  
Tongue Cancer ◽  
Cancer Cell Lines ◽  
Fluorescent Imaging ◽  
Cell Phenotype ◽  
Human Tongue

Tumorigenicity and metastatic activity can be visually monitored in cancer cells that were labelled with stable fluorescence. The aim was to establish and validate local and distant spread of subcutaneously previously injected fluorescence transduced human tongue cancer cell lines of epithelial and mesenchymal phenotype in nude mice. A total of 32 four-week-old male athymic Balb/c nude mice were randomly allocated into 4 groups (n=8). A single dose of 0.3 mL PBS containing 1 × 107 of four different cancer cell-lines (UM1, UM1-GFP, UM2, and UM2-RFP) was injected subcutaneously into the right side of their posterolateral back. Validity assessment of the labelled cancer cells’ tumorigenicity was assessed by physical examination, imaging, and histology four weeks after the injection. The tumor take rate of cancer cells was similar in animals injected with either parental or transduced cancer cells. Transduced cancer cells in mice were easily detectable in vivo and after cryosection using fluorescent imaging. UM1 cells showed increased tumor take rate and mean tumor volume, presenting with disorganized histopathological patterns. Fluorescence labelled epithelial and mesenchymal human tongue cancer cell lines do not change in tumorigenicity or cell phenotype after injection in vivo.

scholarly journals Identification of Prostaglandin F2 Receptor Negative Regulator (PTGFRN) as an internalizable target in cancer cells for antibody-drug conjugate development

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0246197
Author(s):  
Jorge Marquez ◽  
Jianping Dong ◽  
Chun Dong ◽  
Changsheng Tian ◽  
Ginette Serrero
Keyword(s):  
Flow Cytometry ◽  
Western Blot ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Negative Regulator ◽  
Target Validation ◽  
Antibody Drug

Antibody-drug conjugates (ADC) are effective antibody-based therapeutics for hematopoietic and lymphoid tumors. However, there is need to identify new targets for ADCs, particularly for solid tumors and cancers with unmet needs. From a hybridoma library developed against cancer cells, we selected the mouse monoclonal antibody 33B7, which was able to bind to, and internalize, cancer cell lines. This antibody was used for identification of the target by immunoprecipitation and mass spectrometric analysis, followed by target validation. After target validation, 33B7 binding and target positivity were tested by flow cytometry and western blot analysis in several cancer cell lines. The ability of 33B7 conjugated to saporin to inhibit in vitro proliferation of PTFRN positive cell lines was investigated, as well as the 33B7 ADC in vivo effect on tumor growth in athymic mice. All flow cytometry and in vitro internalization assays were analyzed for statistical significance using a Welsh’s T-test. Animal studies were analyzed using Two-Way Analysis of Variance (ANOVA) utilizing post-hoc Bonferroni analysis, and/or Mixed Effects analysis. The 33B7 cell surface target was identified as Prostaglandin F2 Receptor Negative Regulator (PTGFRN), a transmembrane protein in the Tetraspanin family. This target was confirmed by showing that PTGFRN-expressing cells bound and internalized 33B7, compared to PTGFRN negative cells. Cells able to bind 33B7 were PTGFRN-positive by Western blot analysis. In vitro treatment PTGFRN-positive cancer cell lines with the 33B7-saporin ADC inhibited their proliferation in a dose-dependent fashion. 33B7 conjugated to saporin was also able to block tumor growth in vivo in mouse xenografts when compared to a control ADC. These findings show that screening antibody libraries for internalizing antibodies in cancer cell lines is a good approach to identify new cancer targets for ADC development. These results suggest PTGFRN is a possible therapeutic target via antibody-based approach for certain cancers.

scholarly journals ETHNOPHARMACOLOGICAL EVALUATION OF MEDICINAL PLANTS FOR CYTOTOXICITY AGAINST VARIOUS CANCER CELL LINES

2017 ◽  
Vol 9 (5) ◽  
pp. 198 ◽  
Author(s):  
Ruchi Singh Thakur ◽  
Bharti Ahirwar
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Fruit Juice ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Phytochemical Analysis ◽  
Phyllanthus Emblica ◽  
Hydroalcoholic Extract

Objective: To evaluate the cytotoxic potential of leaves and seeds of Hibiscus sabdariffa L., fruit juice of Phyllanthus emblica, rhizomes of Dryopteris cochleata and flowers of Caesalpinia decapetala (Roth) Alston along with the chemical profiling of the most toxic extract through Gas-mass spectroscopy-MS technique.Methods: The hydroalcoholic extract of the selected crude drugs was prepared by maceration method and the extracts were undergone through phytochemical analysis. The cytotoxic activity of the hydroalcoholic extract was performed against four cancer cell lines i.e. liver (HepG2), breast (MCF7), prostate (PC-3) and leukemia (HL60) using sulphorhodamine B assay. The hydroalcoholic extract of Caesalpinia decapetala flowers was profiled through using gas mass spectroscopy.Results: The results confirmed that Phyllanthus emblica inhibited HL60 cancer cells at the dose of 35.6 µg/ml and show dose-dependent growth inhibition. The flowers of Caesalpinia decapetala inhibited nearly fifty percent of HL60 cancer cells at very low dose i. e 10 µg/ml. The analysis of Caesalpinia decapetala flowers shows the presence of diterpenoid furanolactones, bufadienolides, polycyclic enones, and androsterone.Conclusion: The fruit juice of Phyllanthus emblica and flowers of Caesalpinia decapetala showed good inhibitory activity against HL60 cancer cell line. The use of Phyllanthus emblica in herbal medicine is justified. The data obtained impelled to further assess the in vivo efficacy of Caesalpinia decapetala flowers for anticancer activity.

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