Prostate cancers ability to invade and grow in bone marrow stroma is thought to be due in part to degradative enzymes. The formation of prostate skeletal metastases have been reproduced in vitro by growing co-cultures of prostatic epithelial cells in bone marrow stroma. Expression of urokinase plasminogen activator, matrix metalloproteinase I and 7 by prostatic epithelial cells were identified using immunocytochemistry. Also, in vivo tissue sections from human prostatic bone marrow metastases were stained. To establish the role of these enzymes on colony formation, inhibitory antibodies directed against urokinase plasminogen activator, matrix metalloproteinase I and matrix metalloproteinase 7 were added into primary prostatic epithelial celts and bone marrow stroma co-cultures. Air prostatic epitherial cell cultures stained positively for matrix metalloproteinase I, matrix metalloproteinase 7 and urokinase plasminogen activator. Generally prostatic epithelial cells derived from malignant tissues showed increased staining in comparison to epithelia derived from non-malignant tissue. In agreement with in vitro cocultures, the in vivo tissue sections of prostate bone marrow metastases showed positive staining for all three enzymes. Inhibition studies demonstrated that blocking matrix metalloproteinase I, matrix metalloproteinase 7 and urokinase plasminogen activator function reduced the median epitheliar colony area significantly in bone marrow stroma co-cultures in vitro. Using a human ex-vivo model we have shown that matrix metalloproteinase I, matrix metalloproteinase 7 and urokinase ptasminogen activator play an important role in the establishment of prostatic epitheliar cells within bone marrow. © 2002 Cancer Research UK.
|Journal||British Journal of Cancer|
|Publication status||Published - 2002|
- Prostatic Neoplasms
- Prostate Cancer