Cancer Biomarkers - Volume 3, issue 4-5

Authors: Mishra, Lopa

Article Type: Editorial

DOI: 10.3233/CBM-2007-34-501

Citation: Cancer Biomarkers, vol. 3, no. 4-5, pp. 169-170, 2007

Authors: Glazer, Robert I. | Wang, Xiaoyang | Yuan, Hongyan | Yin, Yuzhi

Article Type: Research Article

Abstract: Although mammary stem cells were first identified almost two decades ago, recent progress in the characterization of mouse and human mammary stem and progenitor cells has provided new insight into the regulation of their developmental hierarchy. In this review, we discuss the parameters that distinguish stem and progenitor cells from differentiated cells, as well as the signal transduction pathways that drive multilineage expansion. Lastly, we present the utility of modulating stem cell self-renewal through the use of inhibitors of the Notch and Wnt pathways.

Keywords: Mammary tumorigenesis, stem cell antigen-1 (Sca-1), peroxisome proliferator-activated receptor γ (PPARγ), estrogen receptor α, Musashi1

DOI: 10.3233/CBM-2007-34-502

Citation: Cancer Biomarkers, vol. 3, no. 4-5, pp. 171-181, 2007

Authors: Pellicano, Francesca | Holyoake, Tessa L.

Article Type: Research Article

DOI: 10.3233/CBM-2007-34-503

Citation: Cancer Biomarkers, vol. 3, no. 4-5, pp. 183-191, 2007

Authors: Naka, Kazuhito | Ohmura, Masako | Hirao, Atsushi

Article Type: Research Article

Abstract: Stem cells are defined by both their ability to produce stem cells, a property known as self-renewal, and their ability to give rise to differentiated progeny. One of the hallmarks of tissue stem cell is its adoption of a non-dividing, undifferentiated state called quiescence. The ability to sustain quiescence is crucial for stem cell function in several tissues. In this review, we discuss how tissue stem cell properties are affected by the products of tumor-related genes such as ATM, PTEN and FOXO. Recent advances in stem cell research achieved using mouse genetics have provided novel evidence that numerous tumor-related genes, …which are known to control genomic stability, cell proliferation and survival, are also closely associated with the regulation of tissue stem cell self-renewal. These findings support the notion that tissue stem cells and cancer cells share common properties. Further investigation of stem cell regulation by tumor-related genes may pave the way for successful stem cell-based approaches to regenerative medicine and cancer therapy. Show more

Keywords: Tissue stem cell, self-renewal ability, ATM, PTEN, FOXO

DOI: 10.3233/CBM-2007-34-504

Citation: Cancer Biomarkers, vol. 3, no. 4-5, pp. 193-201, 2007

Authors: Buac, Kristina | Pavan, William J.

Article Type: Research Article

Abstract: Melanocytes are pigment-producing cells responsible for coloration of skin and hair. Studies using mouse models have allowed identification of putative melanocyte stem cells within the hair follicle and understanding of hair graying caused by abnormal melanocyte stem cell maintenance. The malignant transformation of melanocytes results in melanoma, the sixth most common cancer in the United States. Recent studies have offered compelling evidence for the existence of cancer stem cells in numerous tumor types, including melanoma. In this review we provide an overview of some of the current findings on follicular melanocyte stem cells, the genetic pathways involved in their regulation …and maintenance, and discuss recent studies that support the existence of cancer stem cells in melanoma. Show more

Keywords: Melanocyte stem cells, melanoma, cancer stem cells

DOI: 10.3233/CBM-2007-34-505

Citation: Cancer Biomarkers, vol. 3, no. 4-5, pp. 203-209, 2007

Authors: Natarajan, Thanemozhi G. | FitzGerald, Kevin T.

Article Type: Research Article

Abstract: In an effort to better understand and address the challenges of cancer research and treatment, a new model of tumorigenesis is being developed – the cancer stem cell model. Building upon traditionl concepts of cancer and stem cells, this model is intended to shed new light on the continued struggle with treatment issues such as tumor drug-resistance and recurrence. This review describes the cancer stem cell model with an emphasis on markers that represent the “stemness” phenotype. A thorough understanding of normal and cancer stem cells is necessary for a prescise delineation of cancer stem cells. The objective of such …an improved delineation is to develop targeted therapy for selective elimination of cancer stem cells with minimal toxicity to normal stem cells. Specific targeting of cancer stem cells has proved to be a significant challenge due to the commonality of many markers between normal and cancer stem cells. However, research in the area of cancer biomarkers is slowly, but steadily, progressing. Show more

Keywords: Cancer stem cells, markers, clinical implications

DOI: 10.3233/CBM-2007-34-506

Citation: Cancer Biomarkers, vol. 3, no. 4-5, pp. 211-231, 2007

Authors: Foshay, K. | Miera, A. | Stuart, A. | Fingland, N. | Mobley, S. | Gallicano, G.I.

Article Type: Research Article

Abstract: The identification of distinct prostate cancer stem cell biomarkers is necessary as researchers attempt to isolate, characterize, and therapeutically target these tumor initiating cells. However, in reading the current literature it is frequently difficult to discern which biomarkers and cellular characteristics identify prostate cancer stem cells as opposed to the general population of prostate cancer cells or normal prostate stem cells. Within this review, we address this issue by dissecting out the cell surface markers, adhesion and cytoskeletal proteins, signaling pathways, epigenetic modifications, and the effects of androgens that are specific to and help to define the prostate cancer stem …cell. Show more

Keywords: Prostate, cancer stem cell, biomarker

DOI: 10.3233/CBM-2007-34-507

Citation: Cancer Biomarkers, vol. 3, no. 4-5, pp. 233-244, 2007

Authors: Kondo, Toru

Article Type: Research Article

Abstract: Both stem cells and cancer cells are thought to be capable of unlimited proliferation. Moreover, a small number of cancer cells express stem cell markers, including CD133 and ATP-binding cassette transporters, by which the cells can pump out specific fluorescence dyes, such as Hoechst33342, as well as anti-cancer drugs, suggesting that either cancer cells resemble stem cells or cancers contain stem cell-like cancer cells, called “cancer stem cells (CSCs)”. Using the common characteristics of tissue-specific stem cells, it was demonstrated that many types of tumors and cancer cell lines contain CSCs, which self-renew, express stem cell markers, and are tumorigenic. …It was also shown that CSCs are resistant to anti-cancer drugs and irradiation. Thus CSCs might be a crucial target for the therapy. Because tumors contain CSCs and recruited normal stem cells, both of which contribute to tumorigenesis, it is difficult to separate CSCs from tumors. By contrast, cancer cell lines do not have any contaminating normal stem cells that quickly loose mulitpotentiality and differentiate in normal culture condition, suggesting that cancer cell lines could be an attractive alternative source of cells for CSC research. In this review I summarize the recent progress in CSC research using cancer cell lines. Show more

Keywords: Cancer stem cells, CD133, side population, floating spheres, cancer cell lines

DOI: 10.3233/CBM-2007-34-508

Citation: Cancer Biomarkers, vol. 3, no. 4-5, pp. 245-250, 2007

Authors: Kitisin, K. | Shetty, K. | Mishra, L. | Johnson, L.B.

Article Type: Research Article

Abstract: The liver has enormous regenerative capacity. Restitution of the liver in response to different injuries involves proliferation of cells at different levels of liver lineage. Mature hepatocytes, which are normally dormant, could undergo rapid replication with a near infinite capacity to proliferate. When the replication of mature hepatocytes is inhibited, a reserve compartment of bipotential hepatic progenitor/stem cells is activated. The degree of activation appears to correlate with the degree of inflammation and stage of chronic liver disease. Deregulation of key regulatory signaling pathways such as transforming growth factor-β, Wnt, hepatocyte growth factor, insulin-like growth factor, transforming growth factor-α and …epidermal growth factor in this progenitor/stem cell population could give rise to HCC. Further understanding of these key signaling pathways and the molecular and genetic alterations associated with HCC could provide major advances in new therapeutic and diagnostic modalities. Show more

Keywords: Hepatocellular progenitor/stem cells, oval cell, regeneration

DOI: 10.3233/CBM-2007-34-509

Citation: Cancer Biomarkers, vol. 3, no. 4-5, pp. 251-262, 2007

Authors: Pishvaian, Michael J. | Byers, Stephen W.

Article Type: Research Article

Abstract: WNT signaling plays a key role in the developing embryo and in the maintenance of a stem/progenitor cell compartment in adult tissues. However, WNT signaling is also believed to play an important role in carcinogenesis. WNT signaling may be activated directly through WNT ligand overexpression, or more often through mutations downstream in the WNT signaling cascade. The common endpoint is an inappropriate expansion of a stem cell compartment and proliferation of more differentiated daughter cells which ultimately acquire additional mutations leading to the development of a malignant, invasive cancer cell. It is likely that WNT signaling is at the core …of many human cancers, but no definitive biomarker of WNT activity has been established. Furthermore, while therapies targeting WNT-responsive gene products such as COX-2 and VEGF have been developed, no therapy directly targeting WNT signaling itself has yet made it into the clinic. We present here a brief summary of the WNT signaling cascade, and focus particularly on markers of WNT activity that have diagnostic, prognostic, or therapeutic relevance. Finally, we propose the development of novel ligands of the steroid hormone family of nuclear receptors to be used as therapies that specifically target and inhibit WNT/β-catenin/TCF-mediated transcriptional activity. Show more

Keywords: WNT, β-catenin, TCF, vitamin D, retinoids, PPARγ

DOI: 10.3233/CBM-2007-34-510

Citation: Cancer Biomarkers, vol. 3, no. 4-5, pp. 263-274, 2007