Cancer stem cells in solid tumors: an overview and new approaches for their isolation and characterization

Tirino, Virginia; Desiderio, Vincenzo; Paino, Francesca; Rosa, Alfredo De; Papaccio, Federica; Noce, Marcella La; Laino, Luigi; Francesco, Francesco De; Papaccio, Gianpaolo

doi:10.1096/fj.12-218222

Cited by 347 publications

(313 citation statements)

References 92 publications

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“…They are a finite population of cancer cells having the unique ability to recapitulate the original tumors and are putatively responsible for the metastatic properties of tumors. 15 TICs are hard to detect and separate even with the most sensitive techniques due to genetic similarity with other tumor cells. Furthermore, methods that rely on specific surface markers for detection are hampered by the lack of a defined genetic fingerprint of target cells even from the same tissue; 16 thus, a pure population of specific cells still cannot be isolated.…”

Section: Introductionmentioning

confidence: 99%

Enhanced contactless dielectrophoresis enrichment and isolation platform via cell-scale microstructures

et al. 2016

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We designed a new microfluidic device that uses pillars on the same order as the diameter of a cell (20 lm) to isolate and enrich rare cell samples from background. These cell-scale microstructures improve viability, trapping efficiency, and throughput while reducing pearl chaining. The area where cells trap on each pillar is small, such that only one or two cells trap while fluid flow carries away excess cells. We employed contactless dielectrophoresis in which a thin PDMS membrane separates the cell suspension from the electrodes, improving cell viability for off-chip collection and analysis. We compared viability and trapping efficiency of a highly aggressive Mouse Ovarian Surface Epithelial (MOSE) cell line in this 20 lm pillar device to measurements in an earlier device with the same layout but pillars of 100 lm diameter. We found that MOSE cells in the new device with 20 lm pillars had higher viability at 350 V RMS , 30 kHz, and 1.2 ml/h (control 77%, untrapped 71%, trapped 81%) than in the previous generation device (untrapped 47%, trapped 42%). The new device can trap up to 6 times more cells under the same conditions. Our new device can sort cells with a high flow rate of 2.2 ml/h and throughput of a few million cells per hour while maintaining a viable population of cells for off-chip analysis. By using the device to separate subpopulations of tumor cells while maintaining their viability at large sample sizes, this technology can be used in developing personalized treatments that target the most aggressive cancerous cells. V C 2016 AIP Publishing LLC. [http://dx

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Section: Introductionmentioning

confidence: 99%

Enhanced contactless dielectrophoresis enrichment and isolation platform via cell-scale microstructures

et al. 2016

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“…On the basis of these characteristics, such as acquired resistance to cytotoxic chemotherapy agents for the overexpression of ATP-binding cassette multidrug efflux transporters 28,32,33 , or for the upregulation of the expression of detoxification enzymes such as ALDH 32 , for the expression of a particular surface marker, such as CD133, CD44, CD34, CD90, and others 30,34,35,41 , several different methods to isolate CSCs have been developed [42][43][44] . One of these techniques is the sphere formation assay, which is based on the capacity of CSCs to grow under non-adherent conditions.…”

Section: Discussionmentioning

confidence: 99%

Establishment of Cancer Stem Cell Cultures from Human Conventional Osteosarcoma

Palmini

Zonefrati

Mavilia

et al. 2016

JoVE

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The current improvements in therapy against osteosarcoma (OS) have prolonged the lives of cancer patients, but the survival rate of five years remains poor when metastasis has occurred. The Cancer Stem Cell (CSC) theory holds that there is a subset of tumor cells within the tumor that have stem-like characteristics, including the capacity to maintain the tumor and to resist multidrug chemotherapy. Therefore, a better understanding of OS biology and pathogenesis is needed in order to advance the development of targeted therapies to eradicate this particular subset and to reduce morbidity and mortality among patients. Isolating CSCs, establishing cell cultures of CSCs, and studying their biology are important steps to improving our understanding of OS biology and pathogenesis. The establishment of human-derived OS-CSCs from biopsies of OS has been made possible using several methods, including the capacity to create 3-dimensional stem cell cultures under nonadherent conditions. Under these conditions, CSCs are able to create spherical floating colonies formed by daughter stem cells; these colonies are termed "cellular spheres". Here, we describe a method to establish CSC cultures from primary cell cultures of conventional OS obtained from OS biopsies. We clearly describe the several passages required to isolate and characterize CSCs.

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“…[20] A breast CSC subpopulation was identified and isolated by the combination of CD44 and CD24 markers. [2] Functional CSC properties like intracellular ALDH enzymatic activities and ABC transporter efflux activities of vital DNA dyes such as Hoechst 33342 have been used for CSC isolation.…”

Section: Cd38mentioning

confidence: 99%

Therapeutic strategies for targeting cancer stem cells

Kim¹,

Siegler²,

Siriwon³

et al. 2016

JCMT

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The therapeutic limitations of conventional chemotherapeutic drugs present a challenge for cancer therapy; these shortcomings are largely attributed to the ability of cancer cells to repopulate and metastasize after initial therapies. Compelling evidence suggests that cancer stem cells (CSCs) have a crucial impact in current shortcomings of cancer therapy because they are largely responsible for tumor initiation, relapse, metastasis, and chemo-resistance. Thus, a better understanding of the properties and mechanisms underlying CSC resistance to treatments is necessary to improve patient outcomes and survival rates. In this review, the authors characterize and compare different CSC-specific biomarkers that are present in various types of tumors. We further discuss multiple targeting approaches currently in preclinical or clinical testing that show great potential for targeting CSCs. This review discusses numerous strategies to eliminate CSCs by targeting surface biomarkers, regulating CSC-associated oncogenes and signaling pathways, inhibiting drug-efflux pumps involved in drug resistance, modulating the tumor microenvironment and immune system, and applying drug combination therapy using nanomedicine.

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Cancer stem cells in solid tumors: an overview and new approaches for their isolation and characterization

Cited by 347 publications

References 92 publications

Enhanced contactless dielectrophoresis enrichment and isolation platform via cell-scale microstructures

Enhanced contactless dielectrophoresis enrichment and isolation platform via cell-scale microstructures

Establishment of Cancer Stem Cell Cultures from Human Conventional Osteosarcoma

Therapeutic strategies for targeting cancer stem cells

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