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Stem-Like Cells Identified in Benign Tumors

Cells have capability of generating new tumors in transplanted animals; show drug resistance Jul 27, 2009 MONDAY, July 27 (HealthDay News) -- Benign tumors contain stem-like cells that can be serially transplanted to generate new tumors, suggesting that such cells in benign as well as malignant tumors may be targets for anti-tumor therapies, according to a study published in the July issue of the British Journal of Cancer. Q. Xu, Ph.D. of Cedars-Sinai Medical Center in Los Angeles, and colleagues isolated stem-like cells from hormone-producing and non-producing pituitary tumors from eight patients and transplanted them into immune-deficient mice. The researchers found that the stem-like cells generated new tumors that were genetically identical to the original tumors, and that the stem-like cells isolated from these new tumors generated genetically identical tumors after transplantation into other mice. They also found that the stem-like cells were resistant to chemotherapy, suggesting that stem-like cells may be partly responsible for cancer relapse in some types of cancer. "The conclusions from this study may have applications to understanding pituitary tumors, as well as implications in cancer stem cell theory in general," the authors conclude. The study was funded in part by the National Institutes of Health and the Italian Association for Neurological Research. Abstract Full Text (subscription or payment may be required) British Journal of Cancer (2010) 102, 789–795. doi:10.1038/sj.bjc.6605551 www.bjcancer.com Published online 26 January 2010 Hypoxia inducible factors in cancer stem cells J M Heddleston1, Z Li1, J D Lathia1, S Bao1, A B Hjelmeland1 and J N Rich1 1Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland 44195, OH, USA Correspondence: Professor JN Rich, E-mail: richj@ccf.org Received 14 October 2009; Revised 8 December 2009; Accepted 22 December 2009; Published online 26 January 2010. Top of pageAbstract Oxygen is an essential regulator of cellular metabolism, survival, and proliferation. Cellular responses to oxygen levels are monitored, in part, by the transcriptional activity of the hypoxia inducible factors (HIFs). Under hypoxia, HIFs regulate a variety of pro-angiogenic and pro-glycolysis pathways. In solid cancers, regions of hypoxia are commonly present throughout the tissue because of the chaotic vascular architecture and regions of necrosis. In these regions, the hypoxic state fluctuates in a spatial and temporal manner. Transient hypoxic cycling causes an increase in the activity of the HIF proteins above what is typical for non-pathologic tissue. The extent of hypoxia strongly correlates to poor patient survival, therapeutic resistance and an aggressive tumour phenotype, but the full contribution of hypoxia and the HIFs to tumour biology is an area of active investigation. Recent reports link resistance to conventional therapies and the metastatic potential to a stem-like tumour population, termed cancer stem cells (CSCs). We and others have shown that within brain tumours CSCs reside in two niches, a perivascular location and the surrounding necrotic tissue. Restricted oxygen conditions increase the CSC fraction and promote acquisition of a stem-like state. Cancer stem cells are critically dependant on the HIFs for survival, self-renewal, and tumour growth. These observations and those from normal stem cell biology provide a new mechanistic explanation for the contribution of hypoxia to malignancy. Further, the presence of hypoxia in tumours may present challenges for therapy because of the promotion of CSC phenotypes even upon successful killing of CSCs. The current experimental evidence suggests that CSCs are plastic cell states governed by microenvironmental conditions, such as hypoxia, that may be critical for the development of new therapies targeted to disrupt the microenvironment.