AAOS Now

Published 12/1/2010
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Mary Ann Porucznik

New model helps researchers find treatments

Rats may hold answer to human dilemma

In approximately 10 percent of the nearly 1.4 million new cases of cancer diagnosed each year, the cancer will metastasize to the spine, reported Camilo A. Molina, BA. Although treatments have improved, much remains to be done, in particular to extend the lives of those patients with breast cancer that has metastasized to the spine.

In more than one in five patients with breast cancer metastatic spine disease, the growing tumor will begin to compress the spinal cord, resulting in pain and paralysis. Current treatment modalities, including surgery, chemotherapy, and radiation, have not been effective—even though diagnostic advances have helped speed identification of those who need treatment.

To find new ways to treat this condition, researchers at Johns Hopkins University School of Medicine sought to create a practical, reproducible, and reliable animal model, using human tumor cell lines. Mr. Molina presented the results of their study, “Development of a Novel Intravertebral Human Breast Adenocarcinoma Rat Model for the Study of Intravertebral Metastatic Spine Disease,” at the 2010 annual meeting of the North American Spine Society.

The researchers used a rat model, and the study involved 14 female nude athymic rats. The researchers transplanted human breast cancer cells into half of the rats and conducted a similar surgery without transplantation on the remaining rats.

Within two weeks, the rats with the transplanted tumor cells began to experience a decline in neurologic function, just as humans with breast cancer metastatic spine disease did. By day 16, the tumor had progressed to the point where the animals were paralyzed, which was defined as the study endpoint. None of the rats in the control group experienced any decline in neurologic motor function.

After euthanizing the rats in the experimental group, researchers conducted a histopathologic and radiographic analysis of the spine and tumor. “The histological analysis showed the spinal cord had been compressed as the cancer cells invaded the spinal canal. In addition, tumor osteolytic activity was observed in the vertebrae, most likely due to invasive factors secreted by the neoplasm,” they wrote.

According to Mr. Molina, the larger rat model provides researchers with an advantage in seeking potential interventions. Additionally, because this model uses actual human tumor cells, researchers will be able to mimic the complex genetic abnormalities in human cells, thus enabling them to target specific therapeutic interventions to various population models.

Mr. Molina’s coauthors include Daniel M. Sciubba, MD; Rachel Sarabia-Estrada, DVM, PhD; and Ziya L. Gokaslan, MD.

Disclosure information: Mr. Molina—Howard Hughes Medical Institute Medical Student Research Fellowship; Dr. Sciubba—DePuy Spine; Dr. Sarabia-Estrada—no conflicts.

Dr. Gokaslau—Spinal Kinetics; U.S. Spinal Tech; Stryker; AO North America; DePuy; Integra; NREF; AO Spine.

Bottom line

  • Researchers need animal models to test treatments before applying those treatments to human patients.
  • This rat model has a larger spine than the previous mouse model, so researchers can deliver interventions more easily.
  • Because human tumor cells are used, researchers can employ this model for future experiments.