The cancer stem cell (CSC) concept has important implications for understanding carcinogenesis as well as for the development of cancer therapeutics. According to this concept, tumors are initiated and maintained by a cellular subcomponent that displays stem cell properties. These properties include self-renewal, which drives tumorigenesis, and differentiation (albeit aberrant), which contributes to tumor cellular heterogeneity. The existence of CSCs has been described in a variety of hematologic and solid tumors including those of the breast, brain, colon, pancreas, lung, liver, and head and neck.

via jci.org

Cancer stem cells (CSC) are thought also to contribute to tumor spread (metastasis) and recurrence after treatment, so many researchers are looking at ways of targeting them therapeutically.

Why is this important? According to the article (click on the jci.org link above to access it):

"In addition to intrinsic pathways regulating stem cell functions, normal and malignant stem cells are regulated by extrinsic signals generated in the microenvironment or CSC niche."

What does this mean in simple terms?   Well, in breast cancer, the niche is composed of immune cells, mesenchymal cells (fibroblasts, endothelial cells etc) and these aspects play a important role in both normal breast development and carcinogenesis. Thus, if the microenvironment plays a critical role in the regulation of CSC growth, then looking at ways of interfering with the processes could affect the very production of CSC's.

One of the therapeutic strategies being pursued to target CSC's involves inhibition of self renewal or survival pathways in these cells. Normal cells die due to a process known as programmed cell death or apoptosis but in cancer, the cells continue to proliferate, thereby producing tumours.

It now appears that critical pathways involved may include NOTCH, Hedgehog, and WNT.  Researchers in Michigan, US and Marseille, France have utlised this knowledge to target human breast cancer stem cells, leading to decreased tumor growth and metastasis in mice xenotransplanted with human breast cancer cells using this approach.

In essence, they found that inhibiting the cell surface protein CXCR1, with either an antibody or a small molecule known as repertaxin, selectively depleted the cancer stem cell population in two human breast cancer cell lines in vitro. Loss of the cancer stem cells was followed by extensive death of many of the remaining tumour cells.

Treatment with repertaxin had similar effects in mice xenotransplanted with human breast cancer cells and cancer stem cells were selectively depleted leading to a reduction in tumor growth and metastasis.

It is possible that strategies targeting CXCR1, the soluble protein that binds to it, or the signaling pathways downstream of it, may provide a new approach to deplete breast cancer stem cells, retarding tumour growth and reducing metastasis.

It will be very interesting indeed to see where this research goes in the future.

Posted via web from sally church's posterous