Submit your event on Cancer Stem Cells to be featured.
Cancer Stem CellsCancer stem cells are a renewable population of cells within the tumor microenvironment. Similar to normal stem cells, cancer stem cells give rise to several cell types including other stem cells and progenitor cells which go on to differentiate guided by intrinsic programs and influenced by extrinsic cues. Within tumors, cancer stem cells are present in a small proportion, however they are responsible for tumor progression and metastasis and are associated with tumor recurrence after therapy. The origin of cancer stem cells is not fully elucidated, and several mechanisms have been proposed including cumulative mutations in normal stem cells or progenitor cells as drivers for cancer stem cell development. Additionally, de-differentiation mechanisms have been implicated in the origin of cancer stem cells as exemplified by the process of epithelial to mesenchymal transition (EMT) in carcinomas. Tumor stromal cells influence the survival and self-renewal of Cancer Stem Cells
The Tumor Microenvironment (TME) contains several cell types including endothelial cells, fibroblasts, mesenchymal stem cells and infiltrating immune cells as well as their derived soluble factors (e.g., cytokines and chemokines) which influence cancer stem cell properties and functions. In turn cancer stem cells, via various signaling mechanisms (e.g., IL-6, PDGF, VEGF and bFGF), modulate the activities and properties of stromal cells to ensure that the TME supports the survival of cancer stem cells, formation of new cancer stem cells and tumor expansion. The mTOR signaling pathway is implicated in the regulation of immune responses and angiogenesis within the TME thus shaping tumor progression and therapeutic responses. Explore the role of mTOR in TME
Cancer Stem Cell MarkersCancer stem cells are believed to underscore tumor heterogeneity and are themselves phenotypically diverse. Expression of specific stem cell markers (e.g., CD44, CD90, CD133) serve to isolate cancer stem cells in several solid tumors, but the specific combination of cellular markers expressed by cancer stem cell types is highly heterogeneous and dependent on the type of tumor and affected tissue. Significant variability in cancer stem cell phenotypes occurs within tumors which may arise through various mechanisms including clonal evolution, phenotype instability and resurgence from dormancy. Find all Cancer Stem Cell Products
EMT and Cancer Stem CellsThe precise mechanisms leading to the development of cancer stem cells are not fully resolved. Several paths to stemness and tumor initiation have been proposed including:
The process of epithelial cell de-differentiation leading to a mesenchymal phenotype has been well described for various carcinoma types including hepatocellular, breast, pancreatic, colorectal carcinoma and more. In carcinoma, hypoxia represents a trigger for the induction of EMT programs leading to the development of stemness. Hypoxia, through the stabilization of HIF-1 alpha and HIF-2 alpha, is a driver for the development and maintenance of cancer stem cells. Review Cellular Response to Hypoxia in Cancer
Induction of HIF signaling, the principal transcriptional regulator of the hypoxic response, is associated with the expression of pluripotency markers, supporting the initiation and maintenance of stem cells. Several transcription factors induced in hypoxia are downstream of HIFs and play key roles in cancer cell-renewal including Oct4, NANOG, and Sox2. Select References Carpino G., Cardinale V., Reid L., Alvaro D. Gaudio E. (2012). Cells of origin and cancer stem cells in cholangiocarcinoma. Transl Gastrointest Cancer. https://doi.org/10.3978/j.issn.2224-4778.2011.11.03 Cheah P. L., Li J., Looi L. M., Teoh K. H., Ong D. B., Arends M. J. (2018). DNA mismatch repair and CD133-marked cancer stem cells in colorectal carcinoma. PeerJ. https://doi.org/10.7717/peerj.5530 Clark, D. W., & Palle, K. (2017). Aldehyde dehydrogenases in cancer stem cells: potential as therapeutic targets. Annals of Translational Medicine. https://doi.org/10.21037/atm.2016.11.82 Fillmore, C., & Kuperwasser, C. (2007). Human breast cancer stem cell markers CD44 and CD24: Enriching for cells with functional properties in mice or in man? Breast Cancer Research. https://doi.org/10.1186/bcr1673 Hatano, Y., Fukuda, S., Hisamatsu, K., Hirata, A., Hara, A., & Tomita, H. (2017). Multifaceted interpretation of colon cancer stem cells. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms18071446 Heiler, S., Wang, Z., & Zöller, M. (2016). Pancreatic cancer stem cell markers and exosomes - The incentive push. World Journal of Gastroenterology. https://doi.org/10.3748/wjg.v22.i26.5971 Lang, D., Mascarenhas, J. B., & Shea, C. R. (2013). Melanocytes, melanocyte stem cells, and melanoma stem cells. Clinics in Dermatology. https://doi.org/10.1016/j.clindermatol.2012.08.014 Lang, S. H., Frame, F. M., Collins, A. T. (2009). Prostate cancer stem cells. J Pathol. https://doi.org/10.1002/path.2478 Mayr, C., Ocker, M., Ritter, M., Pichler, M., Neureiter, D., & Kiesslich, T. (2017). Biliary tract cancer stem cells - Translational options and challenges. World Journal of Gastroenterology. https://doi.org/10.3748/wjg.v23.i14.2470 Mikhail F., Popova A., Polyanskaya E., & Tjulandin S. (2017). Role of Stem Cells in Colorectal Cancer Progression and Prognostic and Predictive Characteristics of Stem Cell Markers in Colorectal Cancer. Current Stem Cell Research & Therapy. https://doi.org/10.2174/1574888X11666160905092938 Moharil RB, Dive A, Khandekar S, Bodhade A. (2017). Cancer stem cells: An insight. J Oral Maxillofac Pathol. https://doi.org/10.4103/jomfp.JOMFP_132_16 Papaccio, F., Paino, F., Regad, T., Papaccio, G., Desiderio, V., & Tirino, V. (2017). Concise Review: Cancer Cells, Cancer Stem Cells, and Mesenchymal Stem Cells: Influence in Cancer Development. Stem Cells Translational Medicine. https://doi.org/10.1002/sctm.17-0138 Romano, M., De Francesco, F., Gringeri, E., Giordano, A., Ferraro, G. A., Di Domenico, M., & Cillo, U. (2016). Tumor Microenvironment Versus Cancer Stem Cells in Cholangiocarcinoma: Synergistic Effects?Journal of Cellular Physiology. https://doi.org/10.1002/jcp.25190 Romano, M., De Francesco, F., Pirozzi, G., Gringeri, E., Boetto, R., Domenico, M. Di, … Cillo, U. (2015). Expression of cancer stem cell biomarkers as a tool for a correct therapeutic approach to hepatocellular carcinoma. Oncoscience. PMCID:PMC4468330 Sin, W. C., & Lim, C. L. (2017). Breast cancer stem cells—from origins to targeted therapy. Stem Cell Investigation. https://doi.org/10.21037/sci.2017.11.03 Schatton, T., & Frank, M. H. (2008). Cancer stem cells and human malignant melanoma. Pigment Cell and Melanoma Research. https://doi.org/10.1111/j.1755-148X.2007.00427.x Templeton, A. K., Miyamoto, S., Babu, A., Munshi, A., & Ramesh, R. (2014). Cancer stem cells: progress and challenges in lung cancer. Stem Cell Investigation. https://doi.org/10.3978/j.issn.2306-9759.2014.03.06 Wang, X., Huang, S., & Chen, J. L. (2017). Understanding of leukemic stem cells and their clinical implications. Molecular Cancer. https://doi.org/10.1186/s12943-016-0574-7 Yamashita, T., & Wang, X. W. (2013). Cancer stem cells in the development of liver cancer. Journal of Clinical Investigation. https://doi.org/10.1172/JCI66024 |
