Mechanisms, hypotheses and questions regarding prostate cancer micrometastases to bone

The morbidity and mortality associated with prostate cancer can almost univ ersally be attributed to the consequences of metastases to the bone. While clinically there have been descriptive reports of these lesions and their d etection by bone scan, there is an embrrassing paucity of reports as to the mechanisms of prostate cancer cell trafficking to the bone, adaptation to the bone environment, pertubation of the normal bone reformation process an d the events leading to cachexia and death. In recent years, there have bee n numerous in vitro studies suggesting that PSA and hK2 may play a signific ant biological role in these events. Also, recent data generated form rever se transcription polymerase chain reaction assays reveal that metastasis to the bone may be an early event which further underscores the need to bette r understand this complex and critically important process. This commentary highlights several general concepts and a few specific issues related to C aP bone metastasis with the intent of revealing numerous opportunities for further investigation and inquiry.