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November 08, 2011

Cancer stem cells revealing their many secrets

by Lisa Willemse

Caarts_cancerheartsyou_webLast week, Statistics Canada released a report with figures detailing the cause of death in which it noted that, for the first time, cancer had eclipsed heart disease as the leading cause of death in every province and territory in the country. According to the report, cancer accounted for 30% of all deaths in Canada in 2008. Worldwide, cancer can be attributed to 13% of all deaths.

It seems a fitting time to review some of the latest findings on stem cells and cancer.

While the concept of cancer stem cells is relatively new and still debated in some circles, recent studies reveal a number of secrets that better identify and characterize these cells -- bolstering arguments in support of cancer stem cells as a therapeutic target.

Skin cancer shows parasitic tendencies 
A European-based research team announced findings late last month that implicate a blood vessel formation molecule known as vascular endothelial growth factor – or VEGF – in the growth of skin tumours. Essentially, by secreting large amounts of VEGF, the cancer stem cells are able to attract endothelial cells and stimulate them to multiply, thereby providing a ready source of oxygen and nutrients for the growing carcinoma. In this ability, the relationship between the cancer and surrounding tissue sounds strikingly familiar to a parasite’s ability to manipulate its host. The team further found that the cancer stem cells were able to use VEGF and a co-receptor -– the protein neuropilin-1 –- to stimulate cancer stem cell renewal and tumour growth. The findings suggest that new therapies that block VEGF and neuropilin-1 may have increased effectiveness in treating certain skin cancers. 

“A needle in a haystack” 
A recent paper in Nature Medicine confirmed for the first time the presence of leukemia stem cells in patients with acute myeloid leukemia (AML) and also identified similarities between these rare cells and that of normal blood stem cells.  These similarities -– a set of genes that were found to be common in both types of stem cells -– were further shown to be predictive of clinical outcome (disease progression or relapse) in patients, and represent a biomarker that could speed the identification of AML in patients as well as providing a potential target for future drug therapies.

Class distinction among colon cancer cells 
Another study published in the journal Cell Stem Cell found three classes of tumour-initiating cells within samples of primary colon cancer. But it’s not a level playing field -– while all three classes exist within the cancer stem cell compartment, they are heterogeneous, with one class demonstrably lacking the ability to self-renew or metastasize. The conclusions were that each class of tumour-initiating cell – particularly those that demonstrate the capacity to self-renew and metastasize could be targeted independently.

Brain cancer stem cells have a few tricks up their sleeves
Our understanding of brain cancers – specifically glioblastoma, a deadly and largely untreatable brain tumour – was also enhanced by research at the University of California, Los Angeles, which looked at the glioma stem cells’ metabolism for clues to new treatments. It seems the glioma stem cells are not just complex, they’re incredibly sly as well. The team reported that the metabolism of glioma stem cells is markedly different from those of their progeny; that the cells possess the ability to change their metabolic state if stressed; and generally take up less glucose than regular cancer cells, thereby enhancing their ability to avoid detection. They further found that glioma stem cells are resistant to radiation, one of the most common conventional therapies. The findings help to explain the glioblastoma’s intractability, but also provide a potential new way to identify them and develop targeted treatments.

Image: Cancer Hearts You (breast cancer tumour-initiating cell) by Craig Aarts

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Another new finding to add: a proof-of-concept study that identified an antibiotic - tigecycline, normally used to treat skin and abdominal infections - as having the ability to destroy leukemia cells by shutting down their energy production. http://www.cell.com/cancer-cell/abstract/S1535-6108(11)00398-9

Interesting!

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