A Marker for Cancer Stem Cells that Might Also Lead to a Cell-Killing Treatment

At least some forms of cancers are generated and supported by a small population of cancer stem cells, a malfunctioning, rapidly growing mirror of the healthy tissue environment in which large number of somatic cells are supported by a small number of stem cells. It is the presence of these cancer stem cells that makes it challenging to permanently clear cancer from a patient - if only a few such cells survive, the cancer will return, and the present generation of cancer treatments cannot reliably remove 100% of the targeted cells. Looking on the bright side, if a method of selectively targeting and destroying cancer stem cells could be developed, then this could be a very useful approach to cancer therapeutics. While it is still up for debate as to what degree of useful, exploitable similarity exists between the cancer stem cells that have been identified in cancers of various different types, the research here makes for interesting reading in this context. It strongly suggests that these similarities exist and are broadly present in many tissue types.

"Cancer stem cells", also known as tumor-initiating cells (TIC), appear to cause relapses after radiation and chemotherapy because a single surviving TIC can cause a new tumor to grow. In addition, they appear to be the main cause of metastasis. Effective tumor treatment must therefore aim to kill off TICs as extensively as possible. To this end, a "probe" that marks these cancer stem cells would be useful so that they become visible. Although there are markers that also recognize TICs associated with some types of cancer, no universal, selective probe for cancer stem cells has been found.

Researchers have now succeeded in finding such a probe. They were able to show that their new probe, a fluorescent dye, selectively stains TICs from a broad variety of cancers, including tumors of the lung, central nervous system, breast, kidney, ovary, colon, and prostate, as well as melanomas. Healthy cells and "ordinary" tumor cells were not marked. At high concentrations, the dye also demonstrates considerable cytotoxicity toward TIC, while other cells are barely affected.

The researchers discovered that their probe, named TiY (for tumor-initiating cell probe yellow), recognizes vimentin, which is a molecule in the cytoskeleton. Vimentin is more concentrated in epithelial cells when they transform into mesenchymal cells. Epithelial cells form the tissue that covers the inner and outer surfaces of the body, forming a boundary with the environment. The cells are polar, meaning that the side facing toward the underlying tissue and the side directed outward toward the lumen are different. The cells are also firmly integrated into the cell wall. When they transform into mesenchymal cells, they lose their polarity, are freed from the cell structure, and may wander. This process plays an important role in the development of embryos and healing of wounds. It is also involved in the metastasis of tumors.

Link: https://www.eurekalert.org/pub_releases/2018-04/w-mfc040418.php


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