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Title: Growth factors involved in the skeletal metastases of prostate cancer
Author: Lang, Shona
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1995
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Prostate cancer selectively metastasises to the axial skeleton where it produces osteoblastic lesions. Media conditioned by human osteoblast-like cells demonstrated growth stimulation of prostate cell lines in a dose dependent manner. PC-3 cells were stimulated to a maximum of 3.5 fold greater than control levels. DU145 cells and LNCaP were stimulated to a lesser extent, 2.3 (p<0.025) and 1.5 fold (p<0.025) respectively. This stimulatory activity was heat and acid sensitive and its production from the osteobast-like cells was unaffected by 1nM dihydrotestosterone or 1nM 1,25 (OH)2 vitamin D. Media conditioned by red bone marrow, derived from proximal femora, did not stimulate the growth of prostate cell lines. Prostate cell line growth was also unaffected by media conditioned by cell lines derived from bladder, lung and kidney (diluted to 50%), which represent other metastatic sites of prostate cancer. To aid the characteristation of prostate mitogens in osteoblast-like cell conditioned medium, the effect of haematopoietic growth factors (produced predominantly in the bone environment) was tested. Results showed that PC-3 and DU145 could be significantly (p<0.0025) stimulated by rEPO (>1mIU/ml) and rGM-CSF (>0.1IU/ml) in serum free medium. Stimulation was dose dependent. rEPO stimulated PC-3 cell growth 2.6 fold and DU145 2.2 fold. rGM-CSF stimulated growth of the two cell lines by a greater degree, PC-3 cells were stimulated 3 fold and DU145 2.3 fold. Growth of the same cell lines was unaffected by incubation with rIL-3 (0.1-1000mU/ml) or rG-CSF (0.1-1000IU/ml). The LNCaP cell line was stimulated only by rGM-CSF (>5IU/ml).
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available