Thursday, 25 November 2010

Cancer’s conversions

A developmental transition may be a useful model for tumor progression.

Until recently, the universally accepted dogma in cancer research stated that replicating cells accumulate several rounds of mutations before becoming cancerous. According to that dogma, the mutations that result in metastatic spread throughout the body occur late in tumor progression. This idea has recently been challenged by the identification of cancer stem cells (CSCs), which provide a new explanation for both the initiation and propagation of tumorigenesis. Rather than following a linear process that starts with unchecked replication and ends with the loss of adhesion molecules that drives metastasis, CSCs can self-renew, proliferate, differentiate, and even revert back to a stem cell state, producing metastatic cells at unexpected stages of the disease.

With a new understanding that cancer progression does not necessarily follow a particular order, researchers have been looking for models to help explain how and when cancers become aggressive. While the idea of CSCs helps explain some observations that do not fit within the accepted dogma, researchers have proposed another idea based on a normal process in embryonic development called the epithelial-to-mesenchymal transition (EMT). Embryonic development requires epithelial cells to change gene expression patterns, lose their adhesion molecules, and become motile, mesenchymal-like cells that invade the extracellular matrix and later differentiate to form the interior tissues of the body such as skeletal muscles and the heart. A similar process, which includes the loss of adhesion molecules and the activation of common genes by Wnt/β-catenin and other signaling pathways, is also a prerequisite for malignant tumor development, particularly the metastatic process. Studying the basic biology of EMT, therefore, could shed light on the processes that cancer cells undergo as they develop.

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