Bone Marrow: A Magnet for Spreading Cancer Cells
Marrow is a “metastatic niche”
Prostate cancer (PCa) and breast cancer (BCa) have some key features in common:
- When found early and properly treated, survival rates for each are very high
- Prostate and breast tumors tend to be hormone dependent (androgens for prostate, estrogen for breast)
- If treatment of the local tumor fails, both cancers can spread invasively
- Both cancers have a preference for spreading to bone marrow.
If PCa or BCa tumor cells break away from the primary tumor and enter the blood or lymph system, they are called disseminating tumor cells, or DTCs. These can circulate as single cells or small clusters, and later establish themselves as a tumor in a distant site. One of these sites is bone marrow, which offers resources that draw PCa or BCa DTCs like a magnet draws iron shavings.
The magic of bone marrow makes it attractive to DTCs
Bone marrow is almost magical in terms of what it can do. It is a soft, spongy tissue in the hollow spaces of bones, and can be considered an organ because of what it does. It has its own blood supply, since it contains many blood vessels and capillaries. Its primary function is to manufacture new blood cells. In order to fulfill its job, it contains two types of stem cells:
- Hemopoietic, which can produce blood cells
- Stromal, which can produce fat, cartilage and the kind of cells used to model new bone to replace old bone cells.
The stem cells exist in a nurturing environment, or marrow niche, that not only helps them thrive, but also gives them some of the “messages” that direct what they will become. This transformation of raw material into specific types of cells is where the magic comes in, and it can’t happen without the marrow niche. However, it’s precisely the qualities of the marrow niche that make it attractive to DTCs.
According to Shiozawa, et al. (2015), “It is now known that malignant cells that disseminate to and develop in the bone marrow do so by hijacking the bone marrow niche.”1 The authors explain that this niche presents a fertile soil to PCa and BCa cells that are especially drawn to it. Not only do the DTCs implant themselves there, but they also cause biochemical changes in the niche that “preferentially cater to malignant cells.” By doing so, they derail the ability of the stem cells to become normal cells.
The exact mechanisms by which the tumor cells take advantage of the hospitable marrow niche are not yet fully understood. For instance, there is some evidence that prostate cancer tumor cells can evolve to mimic bone tissue,2 but does this imply that they can “trick” their way in? Much research effort is being poured into this. Perhaps decoding the biology involved on both sides (the niche and the DTCs) will contribute to the development of new therapies that would prevent metastasis to bone.
MRI-guided Focused Ultrasound (MRgFUS) to treat bone mets
Today, a cure for metastatic PCa or BCa does not yet exist. However, there is an effective treatment that can destroy individual metastatic bone tumors and relieve the pain they cause. It is called MRI-guided Focused Ultrasound (MRgFUS). This outpatient treatment involves no surgery or radiation. Instead, under MRI guidance, beams of ultrasound are aimed at the bone tumor from numerous directions. These beams pass harmlessly through skin and other normal tissue, but when they precisely meet at the tumor, they create sufficient heat to destroy the tumor and its nerves that send pain signals to the brain.
1 Shiozawa Y, Eber MR, Berry JE, Taichman RS. Bone marrow as a metastatic niche for disseminated tumor cells from solid tumors. Bonekey Rep. 2015 May 20;4:689.
- Bone mets