Neural Tumor-Initiating Cells Have Distinct Telomere Maintenance and Can be Safely Targeted for Telomerase Inhibition by Pedro Castelo-Branco and 12 co-authors, including
Uri Tabori,
Clin Cancer Res 2011(Jan 1); 17(1): 111-121 [
Full text]. Translational Relevance:
Pediatric neural tumors (brain tumors and neuroblastoma) are the leading cause of morbidity and mortality in childhood cancer. This is due to their ability to recur after minimal disease is achieved. Telomerase is active in most malignant pediatric neural tumors. Therefore, telomerase inhibition may offer an effective treatment option for such patients. Because normal stem cells may require telomerase for continuous self-renewal, this therapy may have devastating effects on normal nervous system development and maintenance.
This study reveals that telomerase activation exists only in the tumor-initiating cancer subpopulation and is critical to sustain their survival and self-renewal potential. Importantly, normal neural or neural crest stem cells do not require telomerase for their self-renewal. Furthermore, as opposed to conventional chemoradiation therapies, telomerase inhibition results in irreversible loss of self-renewal capacity of tumor initiating cells in vitro and in vivo.
These observations uncover a difference between normal and cancer stem cell biology in the nervous system and suggest that telomerase inhibition may offer a specific and safe therapeutic approach for these devastating tumors.
For a commentary on this article, see:
Anita B Hjelmeland and
Jeremy N Rich,
Clin Cancer Res 2011(Jan 1); 17(1): 3-5 (unlike the article, the commentary is not publicly accessible). Abstract:
Telomerase is an important mechanism by which cancers escape replicative senescence. In neural tumors, cancer stem cells express telomerase, suggesting that this may explain their preferential tumorigenesis. Oligonucleotide telomerase targeting selectively disrupts cancer stem cell growth through the induction of differentiation, adding to the armamentarium of anticancer stem cell therapies.
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See also: Geron Announces Publication Demonstrating Activity of Imetelstat Against Cancer Stem Cells From Pediatric Neural Tumors, Business Wire, January 10, 2011.
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ReplyDeleteamazing papers and its really helpful and it always make me curious to read on this "silent attacker cells"
Deletewow!! amazing papers ..
ReplyDeleteI really liked your article, helped me a lot to understand the difference
ReplyDeleteDifference between Tumor Cells and Normal Cells. Contact inhibition is the natural process of arresting cell growth when two or more cells come into contact with each other. Contact inhibition controls cell growth by allowing cells to replicate as old cells die but keeps unnecessary tissues from forming in their place. Normal cells have their own identity and obey the rule of contact inhibition. Normal cells adhere to each other and expire at the end of their life cycles. Tumor cells typically lose these properties and thus grow in an uncontrolled manner even when in contact with neighboring cells. Tumor cells do not follow the rules of contact inhibition, adherence and self-destruction (apoptosis, programmed cell death). Usually, tumor cell contain faulty DNA and chromosomes (some chromosomes may be duplicated or deleted). Tumor cells spread through the body via the lymphatic and circulatory systems. Clearly, tumor cells evade the immune system. Unlike normal cells that are specialized, tumor cells are non-specialized and do not contribute to the functioning of a body part. Normal cells have specialized behaviors and serve a purpose. Tumor cells have lost their specialized function. The first tumor cells (in the human body) are not very malignant cells; subsequent (mature) tumor cells are extremely malignant cells. Ordinarily, old normal cells undergo apoptosis, a series of enzymatic reaction that lead to the death of the cell. Normal cells will self-destruct if genetic / chromosomal abnormalities are found. Tumor cells fail to undergo apoptosis. Normal cells divide about 50 times and then stop dividing and die. Tumor cells can enter the cell cycle repeatedly, and in this way, they are potentially immortal. According to the Ferromagnetic Theory of Cancer / Carcinogenesis / Oncogenesis / Tumorigenesis (Iron Conception), any tumor cells are cells with numerous intracellular superpara-, ferri- and ferromagnetic nanoparticles. Any normal cells are cells with non-numerous intracellular superpara-, ferri- and ferromagnetic nanoparticles. Any cancer and ALS work by these nanoparticles. Tumor cells (cells with these nanoparticles; excessively negatively charged cells) do not follow the rules of contact inhibition and adherence. Enzyme activity can be affected by these nanoparticles (immortality of tumor cells). The immune system does not identify these nanoparticles within cellular organelles (the immune system can’t distinguish between dia-, para-, superpara-, ferri- and ferromagnetic micro- and nano-objects). These nanoparticles can chaotically-anarchically distort DNA and shift chromosomes by local magnetic fields (mistakes in DNA; chromosomal faults; deformed mitoses; non-specialization and ugliness of tumor cells). Oncologists-clinicians must beat cancer (a subtle iron disease) by non-complicated anti-iron methods of The Old Testament.
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