image: Left shows medulloblastoma tumor (green) from untreated mouse. Right shows brain tissue from mouse treated with bFGF lacks tumor growth. view more
Credit: Sanford-Burnham Medical Research Institute
Cancers arise when a normal cell acquires a mutation in a gene that regulates cellular growth or survival. But the particular cell this mutation happens in—the cell of origin—can have an enormous impact on the behavior of the tumor, and on the strategies used to treat it.
Robert Wechsler-Reya, Ph.D., professor and program director at Sanford-Burnham Medical Research Institute, and his team study medulloblastoma, the most common malignant brain cancer in children. A few years ago, they made an important discovery: medulloblastoma can originate from one of two cell types: 1) stem cells, which can make all the different cell types in the brain, or 2) neuronal progenitor cells, which can only make neurons.
Stem cells and progenitor cells are regulated by different growth factors. So, Wechsler-Reya thought, maybe the tumors arising from these cells respond differently to different therapies…
In a study published in the journal Oncogene, he and his team show that this is indeed the case. They looked at one growth factor in particular—basic fibroblast growth factor (bFGF)—and found that while it induces stem cell growth, it also inhibits neuronal progenitor cell growth.
What's more, the researchers discovered that bFGF also blocks the growth of tumors that originate from progenitors. When they administered bFGF into a mouse model of medulloblastoma, it dramatically inhibited tumor growth.
Although bFGF itself can't be used as a drug (it would cause too many off-target effects), this study suggests that molecules like it might be used to treat medulloblastoma—but only for tumors that have the appropriate origins.
"Medulloblastomas are not all alike, and the same is true for cancers of the breast, prostate and other tissues. It's critical for us to figure out how tumors differ from one another, so we can find ways to personalize cancer diagnosis and come up with treatments that are more effective and less harmful," Wechsler-Reya says.
This study was funded by the California Institute for Regenerative Medicine (Leadership Award LA1-01747), the U.S. National Institutes of Health (National Institute of Mental Health grant MH67916), and the Pediatric Brain Tumor Foundation of the U.S.
Original paper:
Emmenegger BA, Hwang EI, Moore C, Markant SL, Brun SN, Dutton JW, Read TA, Fogarty MP, Singh AR, Durden DL, Yang C, McKeehan WL, & Wechsler-Reya RJ (2012). Distinct roles for fibroblast growth factor signaling in cerebellar development and medulloblastoma. Oncogene PMID: 23045271
About Sanford-Burnham Medical Research Institute
Sanford-Burnham Medical Research Institute is dedicated to discovering the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. The Institute consistently ranks among the top five organizations worldwide for its scientific impact in the fields of biology and biochemistry (defined by citations per publication) and currently ranks third in the nation in NIH funding among all laboratory-based research institutes. Sanford-Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory, and childhood diseases. The Institute is especially known for its world-class capabilities in stem cell research and drug discovery technologies. Sanford-Burnham is a U.S.-based, non-profit public benefit corporation, with operations in San Diego (La Jolla), California and Orlando (Lake Nona), Florida. For more information, news, and events, please visit us at sanfordburnham.org.
Journal
Oncogene