Why prostate cancer cells can metastasize but become dormant
Posted Mar 23 2011 12:00am
Researchers at the University of Michigan now think they can explain how and why prostate cancer cells get into bone and can stay dormant before stimulating the recurrence of prostate cancer.
In an article just published in the Journal of Clinical Investigation , Shiozawa et al. have presented data suggesting that prostate cancer cells are selectively secreted in an area of the bone marrow that is normally associated with the development and growth of cells called “hematopoietic stem cells” (HSCs). These are cells that act as precursors to normal red and white blood cells.
For some reason which is still to be fully understood, prostate cancer cells can stay dormant in this particular environment (known as the “bone marrow niche”) and then they can become active again later, leading to prostate cancer recurrence after a period of months or years. (See also the commentary on a presentation by Vesella at the recent IMPaCT meeting that also addressed this topic.)
What Shiozawa and his colleagues have been able to demonstrate, using a mouse model of metastasis, is that human prostate cancer cells are able to compete cells directly with HSCs for space in the mouse’s bone marrow niche. They have also been able to show that increasing the size of the bone marrow niche leads to promotion of metastasis; by comparison, decreasing the size of the niche size reduces the probability of cell dissemination and therefore metastasis.
There are a variety of potential consequences of this new knowledge:
If the bone marrow niche really does play a central role in metastasis of prostate cancer to bone, then researchers have another new target for drugs that may be able to prevent initiation and progression of bone metastasis.
Such drugs could potentially halt or disrupt the ways in which cancer cells enter or behave in the niche, or they could simply keep the cancer cells from out-competing the stem cells.
What we don’t know yet is equally enticing:
How does the initial tumor cell get into the bone marrow niche?
Once there, how and why does the tumor cell become dormant?
What do to the normal HSCs do when thetumor cells enter the niche?
Can other types of cancer cells that also metastasize to bone (such as breast cancer cells), also go to the niche?
One thing we do know. It is the job of the bone marrow niche, under normal circumstances, to stop HSCs from over-proliferating. Clearly, therefore, when tumor cells get into the bone marrow niche, they are able to co-opt the normal biological processes of the bone marrow niche to stop the proliferation of prostate cancer cells too! But how this happens and why tumor growth can be re-triggered later on is still not understood.
Assuming that other researchers are able to replicate the findings of Shiozawa and his colleagues, this may be a critically important finding towards new and very different therapies for the management of cancers, like prostate cancer, that metastasize to bone.