Die hard: Are cancer stem cells the Bruce Willises of tumor biology?

Cancer Stem Cells (CSC) generally constitute a minor cellular population within tumors that exhibits some capacities of normal Stem Cells (SC). The existence of CSC, able to self-renew and differentiate, influences central aspects of tumor biology, in part because they can continue tumor growth, give rise to metastasis, and acquire drug and radioresistance, which open new avenues for therapeutics. It is well known that SC constantly interacts with their niche, which includes mesenchymal cells, extracellular ligands, and the Extra Cellular Matrix (ECM). These interactions regularly lead to homeostasis and maintenance of SC characteristics. However, the exact participation of each of these components for CSC maintenance is not clear, as they appear to be context- or cell-specific. In the recent past, surface cellular markers have been fundamental molecular tools for identifying CSC and distinguishing them from other tumor cells. Importantly, some of these cellular markers have been shown to possess functional roles that affect central aspects of CSC. Likewise, some of these markers can participate in regulating the interaction of CSC with their niche, particularly the ECM. We focused this review on the molecular mechanisms of surface cellular markers commonly employed to identify CSC, highlighting the signaling pathways and mechanisms involved in CSC-ECM interactions, through each of the cellular markers commonly used in the study of CSC, such as CD44, CD133, CD49f, CD24, CXCR4, and LGR5. Their presence does not necessarily implicate them in CSC biology.

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Cancer Stem Cells in Brain Tumor Biology

Cold Spring Harbor Symposia on Quantitative Biology ◽

10.1101/sqb.2008.73.060 ◽

2008 ◽

Vol 73 (0) ◽

pp. 411-420 ◽

Cited By ~ 56

Author(s):

J.N. Rich ◽

C.E. Eyler

Keyword(s):

Stem Cells ◽

Brain Tumor ◽

Cancer Stem Cells ◽

Tumor Biology

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Lung cancer stem cells: Tumor biology and clinical implications

Asia-Pacific Journal of Clinical Oncology ◽

10.1111/j.1743-7563.2012.01550.x ◽

2012 ◽

Vol 8 (3) ◽

pp. 217-222 ◽

Cited By ~ 4

Author(s):

Fariz NURWIDYA ◽

Akiko MURAKAMI ◽

Fumiyuki TAKAHASHI ◽

Kazuhisa TAKAHASHI

Keyword(s):

Lung Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Tumor Biology ◽

Clinical Implications ◽

Lung Cancer Stem Cells

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Assessment of temozolomide action encapsulated in chitosan and polymer nanostructures on glioblastoma cell lines

Romanian Neurosurgery ◽

10.2478/romneu-2014-0002 ◽

2014 ◽

Vol 21 (1) ◽

pp. 19-30

Author(s):

C. Abrudan ◽

I.S. Florian ◽

A. Baritchii ◽

O. Soritau ◽

S. Dreve ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Cell Lines ◽

Malignant Gliomas ◽

Tumor Biology ◽

The United States ◽

Biologically Active ◽

Polypropylene Glycol ◽

Polymer Nanostructures

Abstract Purpose : Glioblastoma multiforme (GBM) remains one of the most devastating diseases known to mankind and affects more than 17,000 patients in the United States alone every year. This malignancy infiltrates the brain early in its course and makes complete neurosurgical resection almost impossible. Recent years have brought significant advances in tumor biology. Many cancers, including gliomas, appear to be supported by cells with stemlike properties. Nanoparticles are excellent candidates to serve as delivery vectors of drugs or biologically active molecules because of their unique chemical and physical properties that result in specific transportation and deposition of such agents in specific organs and tissues.. In the current study we have investigated the in vitro action of nanostructural systems (temozolomide encapsulated in chitosan and polymer nanostructures) on high-grade gliomaderived cancer stem cells (CSCs), with the intention of developing a new therapy to treat specific brain tumors with increased efficacy and minimal toxicity. In vitro cytotoxicity and apoptosis measurements indicated that the drug/vector combination facilitated the ability of the alkylating drug TMZ to alter the resistance of these cancer stem cells, suggesting a new chemotherapy strategy even for patients diagnosed with inoperable or recurrent malignant gliomas Methods : At the National Institute for R & D of Isotopic and Molecular Technologies form Cluj Napoca were synthesized three types of nanostructures chitosan-TMZ, TMZ-chitosan-PEG (polyethylene glycol), TMZ-chitosan-PPG (polypropylene glycol). Three type of cell lines (Glioma-derived stem, HFL and HUVEC) were treated with the 3 types of nanostructures and the survival rate of the cells was compare to standard therapy (TMZ). Results : The results showed a reduction in the rate of survival of the tumor cells. Cell proliferation assays clearly demonstrate the differences betweenconventional chemotherapy (TMZ) and temozolomide encapsulated in chitosan and polymer nanostructures. Conclusion: Nanostructures like chitosan, PEG, PPG are useful as vectors for drugs transport. Despite combined therapy (surgery, radiotherapy, chemotherapy), currently median patient survival is reduced. The key to improving life expectancy could be an effective therapy targeted, customized for each case. An increasingly important role will be new methods of treatment such as immunotherapy, gene therapy or nanotherapy.

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Cancer Stem Cells and Macrophages: Implications in Tumor Biology and Therapeutic Strategies

Mediators of Inflammation ◽

10.1155/2016/9012369 ◽

2016 ◽

Vol 2016 ◽

pp. 1-15 ◽

Cited By ~ 43

Author(s):

Bruno Sainz ◽

Emily Carron ◽

Mireia Vallespinós ◽

Heather L. Machado

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Cross Talk ◽

Tumor Biology ◽

Cell Types ◽

Tumor Formation ◽

Self Renewal ◽

Numerous Cell ◽

Key Drivers

Cancer stem cells (CSCs) are a unique subset of cells within tumors with stemlike properties that have been proposed to be key drivers of tumor initiation and progression. CSCs are functionally defined by their unlimited self-renewal capacity and their ability to initiate tumor formationin vivo. Like normal stem cells, CSCs exist in a cellular niche comprised of numerous cell types including tumor-associated macrophages (TAMs) which provides a unique microenvironment to protect and promote CSC functions. TAMs provide pivotal signals to promote CSC survival, self-renewal, maintenance, and migratory ability, and in turn, CSCs deliver tumor-promoting cues to TAMs that further enhance tumorigenesis. Studies in the last decade have aimed to understand the molecular mediators of CSCs and TAMs, and recent advances have begun to elucidate the complex cross talk that occurs between these two cell types. In this review, we discuss the molecular interactions that define CSC-TAM cross talk at each stage of tumor progression and examine the clinical implications of targeting these interactions.

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Seeing is Believing: Are Cancer Stem Cells the Loch Ness Monster of Tumor Biology?

Stem Cell Reviews and Reports ◽

10.1007/s12015-010-9194-6 ◽

2010 ◽

Vol 7 (2) ◽

pp. 227-237 ◽

Cited By ~ 22

Author(s):

Justin D. Lathia ◽

Monica Venere ◽

Mahendra S. Rao ◽

Jeremy N. Rich

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Tumor Biology

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Eradicating the Roots: Advanced Therapeutic Approaches Targeting Breast Cancer Stem Cells

Current Pharmaceutical Design ◽

10.2174/1381612826666200317132949 ◽

2020 ◽

Vol 26 (17) ◽

pp. 2009-2021 ◽

Cited By ~ 1

Author(s):

Lili He ◽

Anran Yu ◽

Li Deng ◽

Hongwei Zhang

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Tumor Biology ◽

Therapeutic Strategies ◽

Proliferative Potential ◽

Cancer Therapies ◽

Breast Cancer Stem Cells ◽

Self Renewal ◽

Invasion And Migration

Accumulating evidences have demonstrated that the existence of breast cancer-initiating cells, which drives the original tumorigenicity, local invasion and migration propensity of breast cancer. These cells, termed as breast cancer stem cells (BCSCs), possess properties including self-renewal, multidirectional differentiation and proliferative potential, and are believed to play important roles in the intrinsic drug resistance of breast cancer. One of the reasons why BCBCs cause difficulties in breast cancer treating is that BCBCs can control both genetic and non-genetic elements to keep their niches safe and sound, which allows BCSCs for constant self-renewal and differentiation. Therapeutic strategies designed to target BCSCs may ultimately result in effective interventions for the treatment of breast cancer. Novel strategies including nanomedicine, oncolytic virus therapy, immunotherapy and induced differentiation therapy are emerging and proved to be efficient in anti-BCSCs therapy. In this review, we summarized breast tumor biology and the current challenges of breast cancer therapies, focused on breast cancer stem cells, and introduced promising therapeutic strategies targeting BCSCs.

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The Evolving Concepts of Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma

The Scientific World JOURNAL ◽

10.1155/2014/842491 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 12

Author(s):

Amit Shah ◽

Shilpa Patel ◽

Jigna Pathak ◽

Niharika Swain ◽

Shwetha Kumar

Keyword(s):

Stem Cells ◽

Squamous Cell Carcinoma ◽

Cancer Stem Cells ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Tumor Biology ◽

Treatment Strategies ◽

Current Treatment ◽

Neck Squamous Cell Carcinoma

There is increasing evidence that the growth and spread of cancers is driven by a small subpopulation of cancer stem cells (CSCs)—the only cells that are capable of long-term self-renewal and generation of the phenotypically diverse tumor cell population. CSCs have been identified and isolated in a variety of human cancers including head and neck squamous cell carcinoma (HNSCC). The concept of cancer stem cells may have profound implications for our understanding of tumor biology and for the design of novel treatments targeted toward these cells. The present review is an attempt to conceptualize the role of CSCs in HNSCC—its implication in tumorigenesis and the possible additional approach in current treatment strategies.

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Comparison of tumor biology of two distinct cell sub-populations in lung cancer stem cells

Oncotarget ◽

10.18632/oncotarget.18451 ◽

2017 ◽

Vol 8 (57) ◽

pp. 96852-96864 ◽

Cited By ~ 3

Author(s):

Jianyu Wang ◽

Zhiwei Sun ◽

Yongli Liu ◽

Liangsheng Kong ◽

Shixia Zhou ◽

...

Keyword(s):

Lung Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Tumor Biology ◽

Distinct Cell ◽

Lung Cancer Stem Cells

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Nodal-Induced L1CAM/CXCR4 Subpopulation Sustains Tumor Growth and Metastasis in Colorectal Cancer Derived Organoids.

10.21203/rs.3.rs-48786/v1 ◽

2020 ◽

Author(s):

Donatella Delle Cave ◽

Xavier Hernando Momblona ◽

Marta Sevillano ◽

Gabriella Minchiotti ◽

Enza Lonardo

Keyword(s):

Colorectal Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Tumor Growth ◽

Tumor Biology ◽

Cancer Tissue ◽

Metastatic Phenotype ◽

The Individual

Abstract BackgroundColorectal cancer (CRC) is currently the third leading cause for cancer-related mortality. Cancer stem cells have been implicated in colorectal tumor growth, but their specific role in tumor biology, including metastasis, is still uncertain.MethodsIncreased expression of L1CAM, CXCR4 and NODAL was identified in tumor section of patients with CRC and in Patients-derived-organoids (PDOs). The expression of L1CAM, CXCR4 and NODAL was evaluated using quantitative real-time PCR, western blotting, immunofluorescence, immunohistochemistry and flow cytometry. The effects of the L1CAM, CXCR4 and NODAL on tumor growth, proliferation, migration, invasion, colony-formation ability, metastasis and chemoresistance were investigated both in vitro and in vivo.Results We found that human colorectal cancer tissue contains cancer stem cells defined by L1CAMhigh/CXCR4high expression that is activated by Nodal in hypoxic microenvironment. This L1CAMhigh/CXCR4high population is tumorigenic, highly resistant to standard chemotherapy, and determines the metastatic phenotype of the individual tumor. Depletion of the L1CAMhigh/CXCR4high population drastically reduces the tumorigenic potential and the metastatic phenotype of colorectal tumors.ConclusionIn conclusion, we demonstrated that a subpopulation of migrating L1CAMhigh/CXCR4high is essential for tumor progression. Together, these findings suggest that strategies aimed at modulating the Nodal signaling could have important clinical applications to inhibit colorectal cancer-derived metastasis.

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