Cancer stem cell cells

Blanpain C, Mohrin M, Sotiropoulou PA, Passegue E (2011) DNA-damage response in tissue-specific and cancer stem cells. Cell Stem Cell 8 16-29... 

In the last several years, there has been escalating interest in the idea that cancer stem cells play a central role in tumor formation and spread. The cancer stem cell... 

Keywords Hepatocyte liver progenitor cell TGF-(3 p-catenin cancer stem cell... 

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Ghiba T, Kita K, Zheng YW, Yokosuka 0, Saisho H, Iwama A et al (2006). Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology240-251. 

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Fig. 1. Microenvironmental factors and the invasive process. The primary tumor is a heterogeneous mix of cell populations, further diversified by gradients of blood-borne nutrients, oxygen, and drugs. Hypoxia contributes to treatment resistance, upregulates pro-angiogenic and pro-invasive molecules, and helps to maintain cancer stem-like cell populations. Tumor cells may undergo epithelial-to-mesenchymal transition (EMT), enter blood vessels, and disseminate to distant sites where they extravasate, invade, and colonize the tissues. Once established, the cells may undergo the reverse program (mesen-chymal-to-epithelial transition, MET) and proliferate to form metastases, the major reason for treatment failure.

Li Z, Rich JN (2010) Hypoxia and hypoxia inducible factors in cancer stem cell maintenance. Curr Top Microbiol Immunol 345 21-30... 

Yu H, Zhang CM, Wu YS (2010) Research progress in cancer stem cells and their drug resistance. Chin J Cancer 29 261-264... 

Biddle A, Mackenzie IC (2012) Cancer stem cells and EMT in carcinoma. Cancer Metastasis Rev. doi 10.1007/sl0555-10012-19345-10550... 

Alison MR, Lim SM, Nicholson LJ (2011) Cancer stem cells problems for therapy J Pathol 223 147-161... 

For achieving maximal disaggregation of neurospheres, slightly tilt the Pipetman and press tip against the bottom of the tube to generate a fair amount of resistance. Gently triturate pellet for 50-70 times for embryonic rodent cells and 60-80 times for adult rodent cells and cancer stem cells. 

Winquist RJ, Furey BF, Boucher DM (2010) Cancer stem cells as the relevant biomass for drug discovery. Curr Opin Pharmacol 10 385-390... 

Wang S (2009) Anchorage-independent growth of prostate cancer stem cells. Methods Mol Biol 568 151-160... 

While natural heterogeneity of cancer specimens is well documented, and the ability to isolate hundreds to thousands of cells with techniques such as LCM have allowed microarray analysis of more pure populations, the recent re-introduction of the cancer stem cell theory (24,25) has presented an extreme example of the need to isolate rare populations of cells. Cancer stem cells appear to exist at a frequency on the order of 1 in 1000 cells (26). While obtaining completely pure populations of stem cells remains difficult, highly enriched populations of these cells can be isolated using flow cytometry separating on the basis of the presence of certain specific cell markers. 

One hypothesis is that cancer stem cells are relatively immune to current therapeutic methodologies, due in large part to the fact that these cells divide only infrequently and are generally quiescent. As lliese cells also have the potential to cause the formation of a new cancer, therapeutics targeted to these specific cells would be of immense benefit. The fact that cancer stem cells occur in such low frequency dictates that what may arguably be the most important signature to identify within the tumor is completely lost in most microarray analyses. 

While laser capture microdissection and other related techniques may allow for the generation of relatively homogenous cell populations, most such purification steps will largely eliminate any potential cancer stem cells, because these techniques necessitate the identification of differentiated cell types for isolation. As such, cancer stem cells would frequently be eliminated from analysis, and any cancer stem cells that may be accidentally included in the analysis would be in such low occurrence that their signature would most certainly be missed. 

Each of the aforementioned amplification strategies is of potential use in studying smaller, purer cell populations however, few if any of these techniques are amenable to the study of single cells, which may be necessary if analyzing cancer stem cells. In order to study individual cells, it is necessary to have a technique that is sensitive down to the... 

Clarke MF, Dick JE, Dirks PB et al. Cancer stem cells perspectives on current status and future directions AACR Workshop on Cancer Stem Cells. Cancer Res 2006 66 9339-9344. 

Wang JC, Dick JE. Cancer stem cells lessons from leukemia. Trends Cell Biol 2005 15 494-501. Becker AJ, McCulloch CE, Till JE. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 1963 197 452 54. 

On a final note, an emerging idea in the field of cancer biology is the existence of the cancer stem cell, which may give rise to the phenotypically heterogeneous cellular sub-populations that are often seen in solid tumors (87,88). It has been observed that certain cancer cells exhibit the hallmarks of stem cell-like behavior, with the ability to self-renew and the exhibition of multipotency, allowing for differentiation into multiple cell types. 

Tumorigenic heterogeneity in cancer stem cells evolved from long-term cultures of telomerase-immortalized human mesenchymal stem cells Bums, J.S., Abdallah, B.M., Guldberg, P., Rygaard, J., Schroder, H.D., Kassem, M.(2005). Cancer Res, 15 65 (8) 3126-3135. 

Alison, M. R., and Lovell, M. J. Liver cancer The role of stem cells. Cell Prolif. 38, 407, 2005. 

Program in Cancer Stem Cell Biology Duke-NUS Graduate Medical School Singapore, Singapore... 

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