Recent Metastasis Research

Most cancers kill through metastasis. It isn't the initial malignant tumor but rather the spread of its cells throughout the body to seed more growths that outpaces today's medical toolkit. Absent metastasis, most cancers would be far more controllable and far less deadly, and even last generation treatments like chemotherapy could be made more localized and less taxing on the patient. Thus while a way to block metastasis in a majority of cancers is not a cure, it is a worthwhile stepping stone to aim for. Many of the same considerations come into play as for research aimed at destroying cancer cells: are there common mechanisms involved in the dispersal of malignant cancer cells into the blood system; do these migrating cells have any common surface molecules or other distinguishing traits; how plausible is it to interfere in their activities without impacting normal tissues; and so forth.

Cancer research is well funded in comparison to other fields of medical science. While there is a lot of dead wood and waste, as is always the case given the large amounts of public funding, the field as a whole is heading in the right direction towards a robust suite of next generation treatments. For those of us not expecting a high chance of dealing with cancer for another couple of decades at least, the odds are good that we will have a comparatively smooth ride of it. It will be expensive and unpleasant in comparison to, say, avoiding cancer entirely, but targeted immunotherapies with few side effects and that work to produce cures in near every patient will be the order of the day. Metastatic cells will be sabotaged one way or another - either interrupted in their attempts to escape the primary tumor or chased down by targeted cell killers in the bloodstream. All in all it will be a far cry from today's late detection of cancer, standard treatments of radiotherapy and chemotherapy, and the poor odds faced by many patients.

These two items give a decent view into the sort of investigations into metastasis taking place today. Greater understanding and better tools are emerging as researchers search for ways to intervene in the underlying processes driving metastasis so as to prevent cancers from spreading:

Decoding the emergence of metastatic cancer stem cells

Researchers have mapped how information flows through the genetic circuits that cause cancer cells to become metastatic. The research reveals a common pattern in the decision-making that allows cancer cells to both migrate and form new tumors. Researchers say the commonality may open the door to new drugs that interfere with the genetic switches that cancer must flip to form both cancer stem cells and circulating tumor cells - two of the main players in cancer metastasis. "Though some of the circuits for metastasis have been mapped, this is the first study to examine how cancer uses two of those circuits, in concert, to produce not just cancer stem cells, but also dangerous packs of hybrid stem-like-cells that travel in groups to colonize other parts of the body."

The switch that many cancer cells use to become metastatic is the circuit that governs the epithelial-to-mesenchymal transition, or EMT. The EMT, an important feature in embryonic development and wound healing, allows cells to revert back along their developmental path and take on certain stem-like features that allow them to form new tissues and repair tissue damage. [Researchers examined] the interaction between the three-way EMT switch and a second, well-documented genetic switch that gives rise to cancer stem cells (CSCs). The research showed that the CSC circuit also operates as a three-way switch. In addition, the study found "significant correspondence" between the operation of the two switches, which suggests a mechanism that would confer "stemness" on hybrid E-M cancer cells that are known to travel in packs called circulating tumor cells (CTCs).

The coupling between the two switches shows that two seemingly independent and distinct cellular programs - one that drives migration and a second that drives adaptation and tumorigenesis - are linked. "The existence of a link suggests that we may be able to simultaneously target both processes with innovative new therapies."

Viewing Cancer on the Move: New Device Yields Close-up Look at Metastasis

[Researchers] reported on successful tests that captured video of human breast cancer cells as they burrowed through reconstituted body tissue material and made their way into an artificial blood vessel. "There's still so much we don't know about exactly how tumor cells migrate through the body, partly because, even using our best imaging technology, we haven't been able to see precisely how these individual cells move into blood vessels. Our new tool gives us a clearer, close-up look at this process."

Researchers were able to record video of the movement of individual cancer cells as they crawled through a three-dimensional collagen matrix. This material resembles the human tissue that surrounds tumors when cancer cells break away and try to relocate elsewhere in the body. This process is called invasion. [The researchers] also collected video of single cancer cells prying and pushing their way through the wall of an artificial vessel lined with human endothelial cells, the same kind that line human blood vessels. By entering the bloodstream through this process, called intravasion, cancer cells are able to hitch a ride to other parts of the body and begin to form deadly new tumors.

"Cancer cells would have a tough time leaving the original tumor site if it weren't for their ability to enter our bloodstream and gain access to distant sites. So it's actually the entry of cancer cells into the bloodstream that allows the cancer to spread very quickly." Knowing more about this process could unearth a key to thwarting metastasis.

Comments

There has been some success in dealing with metastasis via interference in the MtROS production using mitochondrial antioxidants such as MitoTEMPO and MitoQ. These substances can be bought already and are relatively safe and tested.

"Metastatic progression of cancer is associated with poor outcome, and here we examine metabolic changes underlying this process. Although aerobic glycolysis is known to promote metastasis, we have now identified a different switch primarily affecting mitochondria. The switch involves overload of the electron transport chain (ETC) with preserved mitochondrial functions but increased mitochondria superoxide production. It provides a metastatic advantage phenocopied by partial ETC inhibition, another situation associated with enhancedsuperoxide production. Both cases involved protein tyrosine kinases Src and Pyk2 as downstream effectors. Thus, two different events, ETC overload and partial ETC inhibition, promote superoxide-dependent tumor cell migration, invasion, clonogenicity, and metastasis. Consequently, specific scavenging of mitochondrial superoxide with mitoTEMPO blocked tumor cell migration and prevented spontaneous tumor metastasis in murine and human tumor models"

http://www.cell.com/cell-reports/pdf/S2211-1247%2814%2900527-0.pdf

Posted by: Arren Brandt at November 1st, 2014 1:32 AM

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