Prostate carcinoma bone-stroma interaction and its biologic and therapeutic implications

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Abstract
The homing of prostate carcinoma to bone is a nonrandom, multistep process. Previous studies have revealed significant insights into how tumor cells can interact with the host microenvironment. In this communication, the author summarizes recent studies from his institution and draws conclusions from data published by others pertaining to the biologic and therapeutic implications of bone metastasis from prostate carcinoma. Tumor models have been established to study cellular interaction between human prostate carcinoma cells and bone stroma under two-dimensional and three-dimensional conditions. At the author's institution, experiments were conducted to show that prostate carcinoma cell growth and survival are enhanced in coculture with pleuripotent bone stromal cells. A cotargeting concept for the treatment of patients with prostate carcinoma bone metastasis is introduced. Both genotypical and phenotypical responses were observed to tumor epithelium when it was cocultured under three-dimensional conditions. A "vicious cycle" that was mediated by soluble and insoluble molecules secreted by tumor and bone may be the key to supporting and sustaining tumor colonization in bone. Cotargeting tumor and stroma has yielded promising results, both in preclinical models of prostate carcinoma bone metastasis and in the clinic with patients who were treated with a dual tumor-targeting and bone-targeting strategy. Understanding and targeting the interaction of tumor cells and bone stroma may improve the prognosis, reduce the suffering, and increase the survival of patients with advanced bone metastasis as a consequence of prostate carcinoma.

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