Breast cancer cells (right) spread toward the hindlimb bone (left), using natural bone-destroying cells (osteoclasts) to continue their advance. (Image courtesy of Yibin Kang)
Cancer patients may benefit from a dual strategy for tackling their disease in a class of molecules called microRNAs. Molecular biology graduate student Brian Ell has revealed that microRNAs — small bits of genetic material capable of repressing the expression of certain genes — may serve as both therapeutic targets and predictors of metastasis, or a cancer’s spread from its initial site to other parts of the body.
MicroRNAs are specifically useful for tackling bone metastasis, which occurs in about 70 percent of late-stage cancer patients. During bone metastasis, tumors invade the tightly regulated bone environment and take over the osteoclasts, cells that break down bone material. These cells then go into overdrive and dissolve the bone far more quickly than they would during normal bone turnover, leading to bone lesions and ultimately pathological conditions such as fracture, nerve compression and extreme pain.
“The tumor uses the osteoclasts as forced labor,” explained cancer metastasis expert in the Department of Molecular Biology Yibin Kang, who is Ell’s adviser. Their research is supported by the National Institutes of Health, the Department of Defense, the Susan G. Komen for the Cure Foundation, the Brewster Foundation and the Champalimaud Foundation.
MicroRNAs can reduce that forced labor by inhibiting osteoclast proteins and thus limiting the number of osteoclasts present, as Kang’s lab observed when mice with bone metastasis injected with microRNAs developed significantly fewer bone lesions. Their findings suggest that microRNAs could be effective treatment targets for tackling bone metastasis. And that’s not all: microRNAs may also help doctors detect the cancer’s spread to the bone, with trials in human patients demonstrating a strong correlation between elevated levels of another group of microRNAs and the occurrence of bone metastasis.
Kang, the Warner-Lambert/Parke- Davis Professor of Molecular Biology, said he ultimately hopes to extend mice experimentation to clinical trials. “In the end, we want to help the patients,” he said.
–By Tara Thean
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