Putting Bone Metastasis in the Spotlight

Posted on September 13th, 2018 by Dr. Francis Collins

When cancers spread, or metastasize, from one part of the body to another, bone is a frequent and potentially devastating destination. Now, as you can see in this video, an NIH-funded research team has developed a new system that hopefully will provide us with a better understanding of what goes on when cancer cells invade bone.

In this 3D cross-section, you see the nuclei (green) and cytoplasm (red) of human prostate cancer cells growing inside a bioengineered construct of mouse bone (blue-green) that’s been placed in a mouse. The new system features an imaging window positioned next to the new bone, which enabled the researchers to produce the first series of direct, real-time micrographs of cancer cells eroding the interior of bone.

The researchers, including Peter Friedl and Eleonora Dondossola, the University of Texas MD Anderson Cancer Center, Houston, had been working to develop a better method for studying bone metastases in animal models of cancer for the last six years. A fluorescent imaging technique called intravital multiphoton microscopy (iMPM) has been used extensively to visualize cancer in soft tissues. However, in order to study bone metastases, the researchers had to figure out a way to enable iMPM to look inside much harder material.

They got a break when Friedl learned about a team, led by Dietmar Hutmacher at Australia’s Queensland University of Technology, that had developed a tissue engineering approach for regenerating bone. He realized that by building miniature, window-equipped bone constructs in mice, his group might be able to set the stage for a new way to visualize the complex interactions between cancer cells and bone. And, as reported recently in Science Translational Medicine, the new approach worked [1].

In normal bone, there’s a balance between bone-creating osteoblasts and bone-destroying osteoclasts. Cancer cells are known to shift the balance in favor of osteoclasts, making space for the cancer to grow, and resulting in painful and debilitating bone loss. To learn more in the new study, Friedl and Dondossola implanted prostate cancer cells into fully developed bone constructs and watched to see what would happen. Their studies revealed bone loss concentrated around osteoclasts near the growing cancer cells.

As further proof of principle for their new imaging approach, the researchers treated the mice with zoledronic acid, a drug used to preserve bone in people with cancer and degenerative bone conditions, such as osteoporosis. Their studies showed that the treatment stopped bone loss and slowed the activity of osteoclasts without reducing their numbers. But, as expected, it did nothing to stall the cancer’s growth.

Next up, the researchers plan to explore the effects of other drugs or drug candidates, which remain less well understood. I’ll look forward to following their progress and the implications it may have for helping to develop better ways of preventing and treating bone metastases.

Reference:

[1] Intravital microscopy of osteolytic progression and therapy response of cancer lesions in the bone. Dondossola E, Alexander S, Holzapfel BM, Filippini S, Starbuck MW, Hoffman RM, Navone N, De-Juan-Pardo EM, Logothetis CJ, Hutmacher DW, Friedl P. Sci Transl Med. 2018 Aug 1;10(452).

Links:

Metastatic Cancer (National Cancer Institute/NIH)

Peter Friedl (MD Anderson Cancer Center, Houston)

Eleonora Dondossola (MD Anderson Cancer Center)

NIH Support: National Cancer Institute