T1150 Role of Cyclooxygenase-2 in Cancer Stem Cell Biology and Effect of COX-2 Inhibitors in Anti-Cancer Therapy Targeting Cancer Stem Cells

2010 ◽  
Vol 138 (5) ◽  
pp. S-499
Author(s):  
Masahiko Tsujii ◽  
Jumpei Kondo ◽  
Tomofumi Akasaka ◽  
Ying Jin ◽  
Yoshito Hayashi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Cell Biology ◽  
Stem Cell Biology ◽  
Anti Cancer ◽  
Cox 2 ◽  
Cox 2 Inhibitors

Molecular Pathogenesis of Sporadic Melanoma and Melanoma-Initiating Cells

2010 ◽  
Vol 134 (12) ◽  
pp. 1740-1749
Author(s):  
Yunyi Kong ◽  
Suresh M. Kumar ◽  
Xiaowei Xu
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cell Biology ◽  
Molecular Basis ◽  
Potential Role ◽  
Genetic Alterations ◽  
Stem Cell Biology ◽  
Prevalent Disease

Abstract Recent advances in molecular genetics and cancer stem cell biology have shed some light on the molecular basis of melanomagenesis. In this review, we will focus on major genetic alterations in the melanoma, particularly pathways involved in cell proliferation, apoptosis, and tumor suppression. The potential role of melanoma-initiating cells during melanomagenesis and progression will also be discussed. Understanding pathogenesis of melanoma may uncover new diagnostic clues and therapeutic targets for this increasingly prevalent disease.

scholarly journals Extracellular Vesicles: Evolving Factors in Stem Cell Biology

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Muhammad Nawaz ◽  
Farah Fatima ◽  
Krishna C. Vallabhaneni ◽  
Patrice Penfornis ◽  
Hadi Valadi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Tumor Microenvironment ◽  
Extracellular Vesicles ◽  
Cell Biology ◽  
Trophic Factors ◽  
Stem Cell Biology ◽  
Cell Fates ◽  
Bidirectional Communication

Stem cells are proposed to continuously secrete trophic factors that potentially serve as mediators of autocrine and paracrine activities, associated with reprogramming of the tumor microenvironment, tissue regeneration, and repair. Hitherto, significant efforts have been made to understand the level of underlying paracrine activities influenced by stem cell secreted trophic factors, as little is known about these interactions. Recent findings, however, elucidate this role by reporting the effects of stem cell derived extracellular vesicles (EVs) that mimic the phenotypes of the cells from which they originate. Exchange of genetic information utilizing persistent bidirectional communication mediated by stem cell-EVs could regulate stemness, self-renewal, and differentiation in stem cells and their subpopulations. This review therefore discusses stem cell-EVs as evolving communication factors in stem cell biology, focusing on how they regulate cell fates by inducing persistent and prolonged genetic reprogramming of resident cells in a paracrine fashion. In addition, we address the role of stem cell-secreted vesicles in shaping the tumor microenvironment and immunomodulation and in their ability to stimulate endogenous repair processes during tissue damage. Collectively, these functions ensure an enormous potential for future therapies.

The Role of Nucleophosmin In Hematopoietic Stem Cells and the Pathogenesis of Myelodysplastic Syndrome

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 95-95 ◽  
Author(s):  
Keisuke Ito ◽  
Paolo Sportoletti ◽  
John G Clohessy ◽  
Grisendi Silvia ◽  
Pier Paolo Pandolfi
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Myelodysplastic Syndrome ◽  
Cell Biology ◽  
De Novo ◽  
Stem Cell Biology ◽  
Hematopoietic Stem

Abstract Abstract 95 Myelodysplastic syndrome (MDS) is an incurable stem cell disorder characterized by ineffective hematopoiesis and an increased risk of leukemia transformation. Nucleophosmin (NPM) is directly implicated in primitive hematopoiesis, the pathogenesis of hematopoietic malignancies and more recently of MDS. However, little is known regarding the molecular role and function of NPM in MDS pathogenesis and in stem cell biology. Here we present data demonstrating that NPM plays a critical role in the maintenance of hematopoietic stem cells (HSCs) and the transformation of MDS into leukemia. NPM is located on chromosome 5q and is frequently lost in therapy-related and de novo MDS. We have previously shown that Npm1 acts as a haploinsufficient tumor suppressor in the hematopoietic compartment and Npm1+/− mice develop a hematologic syndrome with features of human MDS, including increased susceptibility to leukemogenesis. As HSCs have been demonstrated to be the target of the primary neoplastic event in MDS, a functional analysis of the HSC compartment is essential to understand the molecular mechanisms in MDS pathogenesis. However, the role of NPM in adult hematopoiesis remains largely unknown as Npm1-deficiency leads to embryonic lethality. To investigate NPM function in adult hematopoiesis, we have generated conditional knockout mice of Npm1, using the Cre-loxP system. Analysis of Npm1 conditional mutants crossed with Mx1-Cre transgenic mice reveals that Npm1 plays a crucial role in adult hematopoiesis and ablation of Npm1 in adult HSCs leads to aberrant cycling and followed by apoptosis. Analysis of cell cycle status revealed that HSCs are impaired in their ability to maintain quiescence after Npm1-deletion and are rapidly depleted in vivo as well as in vitro. Competitive reconstitution assay revealed that Npm1 acts cell-autonomously to maintain HSCs. Conditional inactivation of Npm1 leads to an MDS phenotype including a profoundly impaired ability to differentiate into cells of the erythroid lineage, megakaryocyte dyspoiesis and centrosome amplification. Furthermore, Npm1 loss evokes a p53-dependent response and Npm1-deleted HSCs undergo apoptosis in vivo and in vitro. Strikingly, transfer of the Npm1 mutation into a p53-null background rescued the apoptosis of Npm1-ablated HSCs and resulted in accelerated transformation to an aggressive and lethal form of acute myeloid leukemia. Our findings highlight the crucial role of NPM in stem cell biology and identify a new mechanism by which MDS can progress to leukemia. This has important therapeutic implications for de novo MDS as well as therapy-related MDS, which is known to rapidly evolve to leukemia with frequent loss or mutation of TRP53. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Gastric Cancer Stem Cells

2008 ◽  
Vol 26 (17) ◽  
pp. 2876-2882 ◽  
Author(s):  
Shigeo Takaishi ◽  
Tomoyuki Okumura ◽  
Timothy C. Wang
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Cell Biology ◽  
Cancer Biology ◽  
Human Cancer ◽  
Immunodeficient Mice

Cancer stem cells are defined as the unique subpopulation in the tumors that possess the ability to initiate tumor growth and sustain self-renewal as well as metastatic potential. Accumulating evidence in recent years strongly indicate the existence of cancer stem cells in solid tumors of a wide variety of organs. In this review, we will discuss the possible existence of a gastric cancer stem cell. Our recent data suggest that a subpopulation with a defined marker shows spheroid colony formation in serum-free media in vitro, as well as tumorigenic ability in immunodeficient mice in vivo. We will also discuss the possible origins of the gastric cancer stem cell from an organ-specific stem cell versus a recently recognized new candidate bone marrow–derived cell (BMDC). We have previously shown that BMDC contributed to malignant epithelial cells in the mouse model of Helicobacter-associated gastric cancer. On the basis of these findings from animal model, we propose that a similar phenomenon may also occur in human cancer biology, particularly in the cancer origin of other inflammation-associated cancers. The expanding research field of cancer stem-cell biology may offer a novel clinical apparatus to the diagnosis and treatment of cancer.

scholarly journals Role of Vibrational Spectroscopy in Stem Cell Research

2012 ◽  
Vol 27 ◽  
pp. 167-184 ◽  
Author(s):  
Ceren Aksoy ◽  
Feride Severcan
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Vibrational Spectroscopy ◽  
Cell Biology ◽  
Cell Types ◽  
Stem Cell Biology ◽  
Label Free ◽  
Monitoring Methods

Recent researches have mainly displayed the significant role of stem cells in tissue renewal and homeostasis with their unique capacity to develop different cell types. These findings have clarified the importance of stem cells to improve the effectiveness of any cell therapy for regenerative medicine. Identification of purity and differentiation stages of stem cells are the greatest challenges of stem cell biology and regenerative medicine. The existing methods to carefully monitor and characterize the stem cells have some unwanted effects on the properties of stem cells, and these methods also do not provide real-time information about cellular conditions. These challenges enforce the usage of nondestructive, rapid, sensitive, high quality, label-free, cheep, and innovative chemical monitoring methods. In this context, vibrational spectroscopy provides promissing alternative to get new information into the field of stem cell biology for chemical analysis, quantification, and imaging of stem cells. Raman and infrared spectroscopy and imaging can be used as a new complimentary spectroscopic approaches to gain new insight into stem cell reseaches for future therapeutic and regenerative medicines. In this paper, recent developments in applications of vibrational spectroscopy techniques for stem cell characterization and identification are presented.

scholarly journals Ovarian cancer stem cells express ROR1, which can be targeted for anti–cancer-stem-cell therapy

2014 ◽  
Vol 111 (48) ◽  
pp. 17266-17271 ◽  
Author(s):  
Suping Zhang ◽  
Bing Cui ◽  
Hsien Lai ◽  
Grace Liu ◽  
Emanuela M. Ghia ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cell Therapy ◽  
Cancer Stem Cell ◽  
Stem Cell Therapy ◽  
Ovarian Cancer Stem Cells ◽  
Anti Cancer

scholarly journals Attributes of Oct4 in stem cell biology: perspectives on cancer stem cells of the ovary

2012 ◽  
Vol 5 (1) ◽  
pp. 37 ◽  
Author(s):  
Chantel Samardzija ◽  
Michael Quinn ◽  
Jock K Findlay ◽  
Nuzhat Ahmed
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cell Biology ◽  
Stem Cell Biology

scholarly journals Cyclooxygenase-2: A Role in Cancer Stem Cell Survival and Repopulation of Cancer Cells during Therapy

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Lisa Y. Pang ◽  
Emma A. Hurst ◽  
David J. Argyle
Keyword(s):  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Cell Biology ◽  
Tumour Growth ◽  
Cyclooxygenase 2 ◽  
Conventional Chemotherapy ◽  
Normal Tissues ◽  
Cox 2

Cyclooxygenase-2 (COX-2) is an inducible form of the enzyme that catalyses the synthesis of prostanoids, including prostaglandin E2 (PGE2), a major mediator of inflammation and angiogenesis. COX-2 is overexpressed in cancer cells and is associated with progressive tumour growth, as well as resistance of cancer cells to conventional chemotherapy and radiotherapy. These therapies are often delivered in multiple doses, which are spaced out to allow the recovery of normal tissues between treatments. However, surviving cancer cells also proliferate during treatment intervals, leading to repopulation of the tumour and limiting the effectiveness of the treatment. Tumour cell repopulation is a major cause of treatment failure. The central dogma is that conventional chemotherapy and radiotherapy selects resistant cancer cells that are able to reinitiate tumour growth. However, there is compelling evidence of an active proliferative response, driven by increased COX-2 expression and downstream PGE2release, which contribute to the repopulation of tumours and poor patient outcome. In this review, we will examine the evidence for a role of COX-2 in cancer stem cell biology and as a mediator of tumour repopulation that can be molecularly targeted to overcome resistance to therapy.

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