Electropotential evaluation as a new technique for diagnosing breast lesions

Faupel, Mark L.; Vanel, D.; Barth, Volker; Davies, Richard J.; Fentiman, Ian S.; Holland, Roland; Lamarque, J L; Sacchini, Virgilio; Schreer, Ingrid

doi:10.1016/s0720-048x(96)01113-8

Cited by 33 publications

(26 citation statements)

References 16 publications

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“…The generation of ionic gradients leads to extracellular ionic current flow and the establishment of endogenous voltage gradients. Normal epithelial cells are highly polarized; however, the membrane potential of tumor cells is often depolarized, and this difference results in a drop in transepithelial potential difference (James et al 1956;Faupel et al 1997). Depolarized tumor cells display in- creased intracellular Na þ levels, stable K þ levels, and Cl 2 and Ca 2þ influx (Yang and Brackenbury 2013).…”

Section: Alterations In Electrical Fieldsmentioning

confidence: 99%

Physical and Chemical Gradients in the Tumor Microenvironment Regulate Tumor Cell Invasion, Migration, and Metastasis

Oudin

Weaver

2016

Cold Spring Harb Symp Quant Biol

158

121

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Cancer metastasis requires the invasion of tumor cells into the stroma and the directed migration of tumor cells through the stroma toward the vasculature and lymphatics where they can disseminate and colonize secondary organs. Physical and biochemical gradients that form within the primary tumor tissue promote tumor cell invasion and drive persistent migration toward blood vessels and the lymphatics to facilitate tumor cell dissemination. These microenvironment cues include hypoxia and pH gradients, gradients of soluble cues that induce chemotaxis, and ions that facilitate galvanotaxis, as well as modifications to the concentration, organization, and stiffness of the extracellular matrix that produce haptotactic, alignotactic, and durotactic gradients. These gradients form through dynamic interactions between the tumor cells and the resident fibroblasts, adipocytes, nerves, endothelial cells, infiltrating immune cells, and mesenchymal stem cells. Malignant progression results from the integrated response of the tumor to these extrinsic physical and chemical cues. Here, we first describe how these physical and chemical gradients develop, and we discuss their role in tumor progression. We then review assays to study these gradients. We conclude with a discussion of clinical strategies used to detect and inhibit these gradients in tumors and of new intervention opportunities. Clarifying the role of these gradients in tumor evolution offers a unique approach to target metastasis.Tumors are highly heterogeneous and this feature compromises treatment efficacy and promotes tumor cell dissemination and metastasis to reduce patient survival. Tumor heterogeneity is driven in part by genetic alterations induced through genomic instability and maintained by the evolutionary selection of these genetically modified cells (Alizadeh et al. 2015). Epigenetic, transcriptional, and posttranslational modifications also contribute significantly to tumor cell diversity. Furthermore, cancer develops within a complex tissue microenvironment that itself fosters tumor heterogeneity through clonal selection as well as via epigenetic reprogramming and modifications of the tumor phenotype. The tumor microenvironment is composed of cellular constituents that include cells of the vasculature, infiltrating immune cells, and resident fibroblasts, adipocytes and nerves, and a noncellular component composed of diverse soluble factors and a highly variable and evolving insoluble extracellular matrix (ECM) (Joyce and Pollard 2009). The composition and organization of the tumor microenvironment vary significantly within and across tumors.One key feature of the noncellular microenvironment is the existence of local chemical and physical gradients that exert profound effects on the tumor phenotype, including its predilection to disseminate. In this regard, metastasis is facilitated by efficient local tumor cell invasion that is fostered by ECM and chemokine/cytokine/growth factor gradients which cooperate to promote the directional migration of the t...

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Section: Alterations In Electrical Fieldsmentioning

confidence: 99%

Physical and Chemical Gradients in the Tumor Microenvironment Regulate Tumor Cell Invasion, Migration, and Metastasis

Oudin

Weaver

2016

Cold Spring Harb Symp Quant Biol

158

121

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“…A variety of bioelectric properties have been used as detection modalities for tumors; these capitalize on cancer cells' distinct electrical impedance [367][368][369][370][371][372][373][374][375][376][377][378][379][380][381] or ion content [382,383]. Zeta potential is also associated with cancer; for example asbestos fibers and sheets of positively-charged materials (but not powders of the same material) induce tumors, probably by acting as a capacitor for bioelectric potential, the positive side corresponding to the electron sink existing at a wound (reviewed in [384]).…”

Section: A Unique Bioelectric Signature Reveals Incipient Cancermentioning

confidence: 99%

Cancer as a disorder of patterning information: computational and biophysical perspectives on the cancer problem

Moore

Walker

Levin

2017

Converg. Sci. Phys. Oncol.

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TOPICAL REVIEWCancer as a disorder of patterning information: computational and biophysical perspectives on the cancer problem IntroductionCancer is well-recognized not only as an extremely pernicious medical problem, but also as a group of phenomena deeply connected to the fundamental questions of evolution, multicellularity, pattern (disregulation, and the interplay between the genome and the environment [1,2]. Two fundamental paradigms currently divide the field. One is that cancer results from disorders of genetics: cancer cells are fundamentally broken due to genomic mutation or instability, and their clonal progeny form tumors and metastases. This view is sometimes called the SMT, somatic mutation theory [3][4][5]. A competing perspective is that of cancer as a circuit disease-a disorder of the complex biophysical, transcriptional, and epigenetic dynamics that regulate cellular state and the ability of cells to cooperate in vivo [6][7][8]. Under this view (sometimes called the tissue organization field theory or TOFT, [9,10]), cancer is akin to a traffic jam [11]-the problem is not a permanent discrete alteration within a founder cell and all of its clonal descendants, but an undesirable stable attractor in the complex network of controls that normally guides anatomical homeostasis [12].The relative merits of the two models have been discussed extensively [10,[13][14][15][16][17] AbstractThe current paradigm views cancer as arising clonally from a degradation of genetic information in single cells. A complementary perspective, originating at the dawn of modern developmental biology, is that cancer is the result of a system disorder of algorithms that normally orchestrate individual cell activities toward specific anatomical structures and away from tumorigenesis. A view of cancer as a disease of geometry focuses on the pathways that allow cells to cooperate to build and maintain large-scale anatomical patterning. Cancer may result when cells stop maintaining higher-order structures and reduce the boundary of their computational selves to a single-cell level, reverting to a unicellular lifestyle in which the rest of the organism is merely part of the environment at the expense of which all living things survive. While this view has been widely discussed, little progress has been made in providing a quantitative, mechanistic framework within which this perspective's specific and unique implications for treatment strategies can be tested and biomedically exploited. Here, we highlight two recent areas of progress which may facilitate much-needed progress on the cancer problem. First, we review the roles that endogenous bioelectrical networks, operating across many tissues in vivo, play as a medium of information processing in tumor suppression, progression, and reprogramming. Second, we provide a primer to the development of computational theory and tools for quantifying the information and causal control structures in cancer and other complex biological systems. Rigorous mathematical formalisms now exist to...

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“…The voltage drop between cancerous and normal tissue might have its origins in the depolarisation of the membrane potential of most tumour cells (Ambrose et al, 1956;Binggeli and Weinstein, 1986), which causes a drop in the transepithelial potential difference in areas in which tumour cells are dividing rapidly. A more polarised epithelium is maintained in normal tissues because epithelial cells remain more hyperpolarised (Faupel et al, 1997). We and others have sought to mimic the endogenous DC EFs between tumour and normal tissue, and to study electrical methods of preventing the directed migration of tumour cells that is an early feature of metastasis.…”

Section: Physiological DC Efsmentioning

confidence: 99%

“…The polarity of the transepithelial potential (TEP), and hence the polarity of the endogenous EF of mammary and prostate ducts, correlates with the direction of their breast-or prostate-tumour cell migration relative to an EF in vitro. (A)The human breast-duct lumen has a potential of 30 mV (positive) with respect to the surrounding tissue; therefore, the lumen represents an anode (Faupel et al, 1997). (B)Conversely, the rat prostate-duct lumen is 10 mV (negative) relative to the surrounding tissue and is therefore a cathode (Szatkowski et al, 2000).…”

Section: Left-right Determinationmentioning

confidence: 99%