Although prostate cancer is the second most common cause of death from cancer in the US, it is not the tumor in the prostate that usually causes death. Rather, death mainly occurs as a result of the tumor spreading to the bones, where it is known as an osteoblastic bone metastasis. Treatments that deprive the tumor of male sex hormones (androgens) are usually effective, but only briefly as the tumors typically develop the ability to grow in the absence of androgens and the diseases progresses. New data, generated using two prostate cancer cell lines that lack expression of androgen receptors and that were derived from the bones of an individual with osteoblastic bone metastases, by Nora Navone and colleagues, at The University of Texas MD Anderson Cancer Center, Houston, have provided new insight into the mechanisms by which prostate cancer osteoblastic bone metastases progress.
The androgen receptor–negative prostate cancer cell lines generated by the authors grew when transplanted into immunocompromised mice and generated osteoblastic bone metastases. A protein known as FGF9 was found to be expressed at higher levels in these cells lines than in other bone-derived prostate cancer cells and induced bone formation in an in vitro organ culture assay. Further, as blocking FGF9 reduced the osteoblastic bone metastases in mice transplanted with the cell lines and FGF9 was found to be expressed in all human prostate cancer osteoblastic bone metastases analyzed, the authors suggest that FGF9 has an important role in prostate cancer progression to osteoblastic bone metastases. The cells lines generated are also likely to be an important preclinical model for researchers developing therapeutics for osteoblastic bone metastases in individuals with prostate cancer.