Nanorobots as sensors for cancer microenvironment

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.

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Nanorobots Sense Local Physiochemical Heterogeneities of Tumor Matrisome

10.26434/chemrxiv.12063420.v1 ◽

2020 ◽

Cited By ~ 1

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.

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Targeting Aberrant Sialylation in Cancer Cells Using a Fluorinated Sialic Acid Analog Impairs Adhesion, Migration, and In Vivo Tumor Growth

Molecular Cancer Therapeutics ◽

10.1158/1535-7163.mct-13-0279 ◽

2013 ◽

Vol 12 (10) ◽

pp. 1935-1946 ◽

Cited By ~ 79

Author(s):

Christian Büll ◽

Thomas J. Boltje ◽

Melissa Wassink ◽

Annemarie M.A. de Graaf ◽

Floris L. van Delft ◽

...

Keyword(s):

Sialic Acid ◽

Tumor Growth ◽

Cancer Cells ◽

Acid Analog

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Silver nanoparticles selectively treat triple‐negative breast cancer cells without affecting non‐malignant breast epithelial cells in vitro and in vivo

FASEB BioAdvances ◽

10.1096/fba.2019-00021 ◽

2019 ◽

Vol 1 (10) ◽

pp. 639-660 ◽

Cited By ~ 4

Author(s):

Jessica Swanner ◽

Cale D. Fahrenholtz ◽

Iliana Tenvooren ◽

Brian W. Bernish ◽

James J. Sears ◽

...

Keyword(s):

Breast Cancer ◽

Silver Nanoparticles ◽

Cancer Cells ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cells ◽

Triple Negative ◽

Breast Epithelial Cells ◽

Malignant Breast

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The Harsh Microenvironment in Early Breast Cancer Selects for a Warburg Phenotype

10.1101/2020.04.07.029975 ◽

2020 ◽

Author(s):

Mehdi Damaghi ◽

Jeffrey West ◽

Mark Robertson-Tessi ◽

Liping Xu ◽

Meghan C. Ferrall-Fairbanks ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Ductal Carcinoma ◽

Selection Pressures ◽

Transcriptional Reprogramming ◽

The Poor ◽

Metabolic Conditions ◽

Malignant Breast

AbstractThe harsh microenvironment of ductal carcinoma in situ (DCIS) exerts strong evolutionary selection pressures on cancer cells. We hypothesize that the poor metabolic conditions near the ductal center foment the emergence of a Warburg Effect (WE) phenotype, wherein cells rapidly ferment glucose to lactic acid, even in normoxia. To test this hypothesis, we subjected pre-malignant breast cancer cells to different microenvironmental selection pressures using combinations of hypoxia, acidosis, low glucose, and starvation for many months, and isolated single clones for metabolic and transcriptomic profiling. The two harshest conditions selected for constitutively expressed WE phenotypes. RNA-seq analysis of WE clones identified the transcription factors NFкB and KLF4 as potential inducers of the WE phenotype. NFкB was highly phosphorylated in the glycolytic clones. In stained DCIS samples, KLF4 expression was enriched in the area with the harshest microenvironmental conditions. We simulated in vivo DCIS phenotypic evolution using a mathematical model calibrated from the in vitro results. The WE phenotype emerged in the poor metabolic conditions near the necrotic core. We propose that harsh microenvironments within DCIS select for a Warburg phenotype through constitutive transcriptional reprogramming, thus conferring a survival advantage and facilitating further growth and invasion.

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Ultrastructural modification of cellular interactions in cancer tumor

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100082455 ◽

1978 ◽

Vol 36 (2) ◽

pp. 318-319

Author(s):

N. P. Dmitrieva

Keyword(s):

Cancer Cells ◽

Human Thyroid ◽

Adjacent Cell ◽

Main Role ◽

Cellular Interactions ◽

Electron Microscopic ◽

Cancer Tumor ◽

Normal Human ◽

Characteristic Features

One of the most characteristic features of cancer cells is their ability to metastasia. It is suggested that the modifications of the structure and properties of cancer cells surfaces play the main role in this process. The present work was aimed at finding out what ultrastructural features apear in tumor in vivo which removal of individual cancer cells from the cell population can provide. For this purpose the cellular interactions in the normal human thyroid and cancer tumor of this gland electron microscopic were studied. The tissues were fixed in osmium tetroxide and were embedded in Araldite-Epon.In normal human thyroid the most common type of intercellular contacts was represented by simple junction formed by the parallelalignment of adjacent cell membranees leaving in between an intermembranes space 15-20 nm filled with electronlucid material (Fig. 1a). Sometimes in the basal part of cells dilatations of the intercellular space 40-50 nm wide were found (Fig. 1a). Here the cell surfaces may form single short microvilli.

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Influence of Platelet Membrane Sialic Acid and Platelet-Associated IgG on Ageing and Sequestration of Blood Platelets in Baboons

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649648 ◽

1993 ◽

Vol 70 (04) ◽

pp. 676-680 ◽

Cited By ~ 24

Author(s):

H F Kotzé ◽

V van Wyk ◽

P N Badenhorst ◽

A du P Heyns ◽

J P Roodt ◽

...

Keyword(s):

Sialic Acid ◽

Life Span ◽

Blood Platelets ◽

Senescent Cell ◽

Platelet Membrane ◽

Antigen Complex ◽

The Mean ◽

Aggregation Of Platelets

SummaryPlatelets were isolated from blood of baboons and treated with neuraminidase to remove platelet membrane sialic acid, a process which artificially ages the platelets. The platelets were then labelled with 111In and their mean life span, in vivo distribution and sites of Sequestration were measured. The effect of removal of sialic acid on the attachment of immunoglobulin to platelets were investigated and related to the Sequestration of the platelets by the spleen, liver, and bone marrow. Removal of sialic acid by neuraminidase did not affect the aggregation of platelets by agonists in vitro, nor their sites of Sequestration. The removal of 0.51 (median, range 0.01 to 2.10) nmol sialic acid/108 platelets shortened their life span by 75 h (median, range 0 to 132) h (n = 19, p <0.001), and there was an exponential correlation between the shortening of the mean platelet life span and the amount of sialic acid removed. The increase in platelet-associated IgG was 0.112 (median, range 0.007 to 0.309) fg/platelet (n = 25, p <0.001) after 0.79 (median, range 0.00 to 6.70) nmol sialic acid/108 platelets was removed (p <0.001). There was an exponential correlation between the shortening of mean platelet life span after the removal of sialic acid and the increase in platelet-associated IgG. The results suggest that platelet membrane sialic acid influences ageing of circulating platelets, and that the loss of sialic acid may have exposed a senescent cell antigen that binds IgG on the platelet membrane. The antibody-antigen complex may then provide a signal to the macrophages that the platelet is old, and can be phagocytosed and destroyed.

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A Combined Nutritional and Immunological Intervention to Activate Natural Cytotoxicity Against Breast Cancer Cells In Vitro and In Vivo

10.21236/ada599265 ◽

2011 ◽

Author(s):

A. C. Ross

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Natural Cytotoxicity

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Tubulin Proteins in Cancer Resistance: A Review

Current Drug Metabolism ◽

10.2174/1389200221666200226123638 ◽

2020 ◽

Vol 21 (3) ◽

pp. 178-185 ◽

Cited By ~ 1

Author(s):

Mohammad Amjad Kamal ◽

Maryam Hassan Al-Zahrani ◽

Salman Hasan Khan ◽

Mateen Hasan Khan ◽

Hani Awad Al-Subhi ◽

...

Keyword(s):

Cell Cycle ◽

Cancer Cells ◽

High Rate ◽

Vinca Alkaloids ◽

Cancer Resistance ◽

New Approach ◽

Natural Sources ◽

Cell Cycle Genes ◽

Cancerous Cells ◽

Β Tubulin

Cancer cells are altered with cell cycle genes or they are mutated, leading to a high rate of proliferation compared to normal cells. Alteration in these genes leads to mitosis dysregulation and becomes the basis of tumor progression and resistance to many drugs. The drugs which act on the cell cycle fail to arrest the process, making cancer cell non-responsive to apoptosis or cell death. Vinca alkaloids and taxanes fall in this category and are referred to as antimitotic agents. Microtubule proteins play an important role in mitosis during cell division as a target site for vinca alkaloids and taxanes. These proteins are dynamic in nature and are composed of α-β-tubulin heterodimers. β-tubulin specially βΙΙΙ isotype is generally altered in expression within cancerous cells. Initially, these drugs were very effective in the treatment of cancer but failed to show their desired action after initial chemotherapy. The present review highlights some of the important targets and their mechanism of resistance offered by cancer cells with new promising drugs from natural sources that can lead to the development of a new approach to chemotherapy.

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