Browsing by Subject "Cancer stem cells"
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- PublicationOpen AccessAdvances in the knowledge of breast cancer stem cells. A review(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Schwarz-Cruz y Celis, Angela; Espinosa, Magali; Maldonado, Vilma; Melendez-Zajgla, JorgeMuch effort has been made by researchers to elucidate the complex biology of breast cancer stem cells (BCSCs), a small subset of breast tumor cells that display stem cell properties, drive tumor initiation, and growth. In recent years, it has been suggested that BCSCs could be responsible for the process of metastasis and the development of drug resistance. These findings make the need to find the distinguishing blend of markers that can recognize only BCSCs of the utmost importance in order to be able to design new targeted therapies. This review will summarize BCSCs’ main features as well as the cell surface markers that are currently used to identify them.
- PublicationOpen AccessCancer stem cell markers CD44v9+/CD133- are associated with low apoptosis in both sporadic and ulcerative colitis-associated colorectal cancers(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Nakagomi, Eriko; Mikami, Tetuo; Funahashi, Kimihiko; Okazumi, Shinichi; Shibuya, Kazutoshi; Hiruta, Nobuyuki; Igarashi, YoshinoriObjective. To elucidate tumor cell behavior associated with cancer stem cell (CSC) marker expression, the expression of CD133, CD44v9, and ALDH1A1, which are considered markers of CSCs, was examined in sporadic and ulcerative colitis (UC)- associated colorectal tumors. Methods. A total of 23 cases of sporadic colorectal cancer and 44 cases of adenoma were collected. Additionally, 22 cancer lesions and 38 dysplasia lesions were selected from 28 colectomy cases of UC with neoplastic lesions. Lesions were examined by immunohistochemistry using primary antibodies against CD133, CD44v9, ALDH1A1, Ki-67, cleaved-Caspase 3, and p53. Results. CD133, CD44v9, and ALDH1A1 showed higher expression in both sporadic and UC-associated tumors than in the normal mucosa. ALDH1A1 expression in sporadic cancer was higher in the right colon than in the left colon (p=0.0089). ALDH1A1 expression in UC-associated cancer was higher in those with longer disease duration than in those with shorter disease duration (p=0.019). The CD44v9+/CD133- region had fewer cleaved-Caspase 3 positive cells in both sporadic and UC-associated cancers. In sporadic cancer, CD133+/ALDH1A1+ regions had fewer apoptotic cells than CD133+/ALDH1A1- regions, while CD133+/ALDH1A1- regions were less proliferative than CD133+/ALDH1A1+ regions in UC-associated cancer. Conclusion. CD44+/CD133- regions were commonly associated with low apoptosis in sporadic and UC-associated cancers; thus, these were considered target areas for CSCs. Additionally, the combination of markers comprising CSCs may differ between sporadic and UC-associated cancers.
- PublicationOpen AccessCancer stem cells in breast cancer(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Dittmer, Jürgen; Rody, AchimThere is increasing evidence that cancer stem cells (CSCs) play a critical role in breast cancer initiation, progression, metastasis and drug resistance. It is thought that they are either generated from normal mammary stem/progenitor cells or from mammary epithelial cells by epithelial-mesenchymal transition. Breast CSCs are characterized by the activation of stemness-related pathways, such as the Notch and Wnt pathways, and by the expression of certain stem cell markers, such as CD44, EpCAM and ALDH1. CSCs form a minor population, whose proportion depends on various factors, including environmental conditions. Since CSCs are highly resistant to chemotherapy, additional treatment of breast cancer patients with CSC- specific drugs, such as salinomycin and gamma- secretase inhibitors which target the Wnt or Notch pathway, respectively, will be required. Interestingly, an equilibrium seems to exist between CSCs and non-stem cancer cells, and there are indications that CSCs can be recruited from non-stem cancer cells. As a consequence, it may be necessary to combine a therapy targeting CSCs with common chemotherapy that targets the bulk tumor to avoid the regeneration of CSCs.
- PublicationOpen AccessCancer stem cells: A new target for cancer therapy(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Li, Qianhui; Wu, Jiayu; Chen, Shuo; Zhao, YangThe introduction of the theory of cancer stem cells (CSCs) has provided a new direction and perspective for our understanding of the nature and origin of tumors. Cancer stem cells are believed to be responsible for the treatment failure, drug tolerance, metastasis, and recurrence of tumors. However, it remains a challenge to identify or isolate tumor stem cells and determine their regulatory mechanisms. Therefore, further understanding of the biological characteristics and functions of CSCs is of great practical significance and value to develop new methods of tumor diagnosis and treatment, and may bring new hope patients with cancer
- PublicationOpen AccessClinical significance of stem cell marker CD133 expression in colorectal cancer(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Wang, Bin-Bin; Li, Zhi-juan; Zhang, Feng-Feng; Hou, Hai-Tao; Yu, Jing-Kui; Li, FengObjective: CD133, a glycoprotein, is expressed in different types of human stem cells and tumor cells. Detection of altered CD133 expression in colorectal cancer tissues could be useful as a marker for the prediction of colorectal tumorigenesis, progression, and prognosis. Methods: A total of 19 fresh and 145 paraffin-embedded tissue specimens from colorectal cancer patients were obtained for detection of CD133 expression using flow cytometry and immunohistochemistry, respectively. The tumorigenic capacity of tumor cells from 19 patients was assessed in nude mice. Association of CD133 expression was then analyzed for clinical significance. Results: The percentage of CD133- positive (CD133+) tumor cell population ranged between 0.84% and16.75% (mean ratio=7.15%) of tumor cells in the 19 freshly isolated tissue samples. CD133 expression in tumor cells was associated with tumor lymph node metastasis (9.81% vs. 3.22%; p=0.013) and poor tumor differentiation (8.32% vs. 5.07%; p=0.043). In the 145 paraffin-embedded samples, CD133+ colorectal cancer was also associated with local recurrence of tumorigenesis (p=0.035) and distant metastasis (p=0.017), while patients with over 5% CD133+ tumor cells exhibited a decreased survival rate (p=0.001). Multivariate COX analysis showed that the depth of tumor invasion, histology, stages, lymph node metastasis, and CD133 expression were all independent prognosis factors for colorectal cancer (p=0.032, 0.011, 0.001, 0.002, and 0.030, respectively). Furthermore, as few as 5,000 CD133+ colorectal cancer HCT116 cellswere sufficient to form tumor xenografts, whereas 1x105 CD133- tumor cells failed to develop tumor xenografts in nude mice. Conclusions: CD133 expression is a useful biomarker for prediction of colorectal cancer progression and survival of patients.
- PublicationOpen AccessDysregulated stemness-related genes in gynecological malignancies(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Mak, Victor C.Y.; Siu, Michelle K.Y.; Wong, Oscar G.W.; Chan, Karen K.L.; Ngan, Hextan Y.S.; Cheung, Annie N.Y.In recent years, much attention has been paid to the concept of cancer stem cells (CSC) and self-renewal related pathways in cancer biology. This review outlines the dysregulated stemness-related genes or transcription factors in gynecological cancers. Hedgehog (Hh) and Notch signaling are important pathways in tissue pattern programming and cell fate determination during embryonic development. Hyperactivation of these two pathways was frequently observed in gynecological malignancies such as ovarian, endometrial and cervical cancers. In contrast, the expression profiles of pluripotency-regulating core transcriptional circuitry: Nanog, Oct4 and Sox2 appear heterogeneous. Among these transcription factors, overexpression of Nanog was found to exert a prominent effect in gynecological tumorigenesis, while dysregulations of Oct4 and Sox2 may vary in a context dependent manner. On the other hand, the isolation of putative CSC illustrates a hierarchy model of tumor heterogeneity, in which only a subset of cells among biologically distinct populations can initiate tumor growth. Re-activation of these pluripotent transcription factors (Nanog, Oct4 and/or Sox2) in association with distinct tumorigenic properties could be found in clones isolated from gynecological tumors using various approaches. Recent understanding on the roles of Hh and Notch signaling in enhancing CSC survival may help to better understand the mechanism of carcinogenesis and identify new pharmaceutical targets for gynecological malignancies
- PublicationOpen AccessHeat shock proteins in cancer stem cell maintenance: a potential therapeutic target?(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Lettini, Giacomo; Lepore, Silvia; Crispo, Fabiana; Sisinni, Lorenza; Esposito, Franca; Landriscina, Matteo
- PublicationOpen AccessHormone receptor status, erbB2 expression and cancer stem cell characteristics of circulating tumor cells in breast cancer patients(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Rack, Brigitte; Bock, Carolin; Andergassen, Ulrich; Doisneau-Sixou, SophieThe most important predictor for disease-free and overall survival of breast cancer patients is the presence of axillary lymph node metastasis. For surveillance during recurrence-free follow-up or in metastatic disease no marker is available at the moment. Several trials have shown the prognostic relevance of circulating tumor cells (CTC) in early and metastatic breast cancers. Indeed, only CTC that exhibit specific molecular characteristics including stem cell characteristics, could be able to create new metastasis. Hormone therapy or anti-erbB2 therapies are prescribed according to the hormone (ERα/PR expression) and erbB2 status of the initial tumor. Nonetheless, it appears that the CTC, and consequently the metastatic cells, may have a very different hormone and erbB2 status. An optimal individualized treatment could then be obtained by characterizing ERα and erbB2 status in the CTC and comparing it to the primary tumor
- PublicationOpen AccessThe emerging role of mTOR up-regulation in brain astrocytoma(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Ryskalin, Larisa; Limanaqi, Fiona; Biagioni, Francesca; Frati, Alessandro; Esposito, Vincenzo; Calierno, Maria Teresa; Lenzi, Paola; Fornai, FrancescoThe present manuscript is an overview of various effects of mTOR up-regulation in astrocytoma with an emphasis on its deleterious effects on the proliferation of Glioblastoma Multiforme. The manuscript reports consistent evidence indicating the occurrence of mTOR up-regulation both in experimental and human astrocytoma. The grading of human astrocytoma is discussed in relationship with mTOR upregulation. In the second part of the manuscript, the biochemical pathways under the influence of mTOR are translated to cell phenotypes which are generated by mTOR up-regulation and reverted by its inhibition. A special section is dedicated to the prominent role of autophagy in mediating the effects of mTOR in glioblastoma. In detail, autophagy inhibition produced by mTOR up-regulation determines the fate of cancer stem cells. On the other hand, biochemical findings disclose the remarkable effects of autophagy activators as powerful inducers of cell differentiation with a strong prevalence towards neuronal phenotypes. Thus, mTOR modulation acts on the neurobiology of glioblastoma just like it operates in vivo at the level of brain stem cell niches by altering autophagy-dependent cell differentiation. In the light of such a critical role of autophagy we analyzed the ubiquitin proteasome system. The merging between autophagy and proteasome generates a novel organelle, named autophagoproteasome which is strongly induced by mTOR inhibitors in glioblastoma cells. Remarkably, when mTOR is maximally inhibited the proteasome component selectively moves within autophagy vacuoles, thus making the proteasome activity dependent on the entry within autophagy compartment.
- PublicationOpen AccessThe involvement of microRNAs in malignant transformation(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Rutnam, Zina Jeyapalan; Yang, BurtonIn the multiple steps in cancer progression, microRNAs (miRNAs) play significant roles in each stage. Reports of considerable differences in expression levels of miRNAs between normal and malignant tissues are understandable considering miRNAs are key regulators of gene expression. Dysregulation of miRNA expression levels in neoplasia occurs because many miRNAs are located in “fragile sites”, which are frequently deleted in cancer. miRNAs are often down regulated in cancerous tissues and target oncogenic proteins are classified as tumour suppressor miRNAs, such as let-7. While, miRNAs that are frequently over-expression in neoplastic tissues compared to normal tissues and regulate tumour suppressor proteins are categorized as "oncomiRs". In this review, we summarize information about microRNAs involved in the emerging field of cancer stem cells, and microRNAs involved in breast cancer, an area of our expertise. The application of miRNAs to cancer therapeutics and diagnostics is emerging as an important field of gene therapy. The diverse nature of miRNAs in cancer is continually being elucidated to lead to the enigmatic treatment options for neoplastic disease.
- PublicationOpen AccessThe role of cancer stem cells and the side population in epithelial ovarian cancer(Murcia : F. Hernández, 2010) Fong, Miranda Y.; Kakar, S.S.Ovarian cancer is the most lethal cancer of the female reproductive tract, accounting for ~15,000 deaths per year according to the National Cancer Institute and American Cancer Society. This review article covers risk factors for the development of ovarian cancer, current detection strategies, prognostic markers, treatment strategies, etiology of tumorigenesis, and ovarian somatic stem cells. While the etiology of ovarian cancer is still unknown, several theories have been proposed as the mechanism of carcinogenesis. One theory states that the surface epithelium undergoing invagination and forming inclusion cysts that are exposed to growth factors and cytokines. The “gonadotropin theory” has also been proposed. Other reigning models for tumorigenesis include the stochastical model where a distinct population of cells acquires somatic mutations leading to metastasis, and the hierarchical model where the tumor is initiated by cancer stem cells (CSCs). CSCs isolated from primary tumors have the ability to regenerate the tumor and reconstitute the original tumor phenotype with as few as 100 cells. CSCs from ovarian carcinomas display the cell surface markers CD44+CD117+CD133+. CSCs are also thought to account for chemotherapy resistance through the expression of highly selective transporters ABCG2 and MDR1 and activation of TLR4/MyD88. The side population has been characterized by their ability to efflux lipophilic substrates, including the dye Hoechst 33342 and many chemotherapy agents. This ability has been attributed to the expression of the transporters ABCG2 and MDR1.