Prostatic adenocarcinoma is virtually unique in its tendency to produce osteoblastic bone lesions. The hypothesis of the present thesis was that the basis of this osteogenic response to skeletal metastases of prostate cancer is mediated by the production of trophic factors from prostatic tissue. I have therefore examined the mitogenic activity of extracts of human prostatic tissue and of some known growth factors in isolated fetal rat osteoblasts, fetal fibroblasts, and osteoblast-derived rat osteosarcoma cells. The results demonstrate that material with characteristics of peptides can be extracted from prostatic tissue and appears distinct from a variety of known growth factors. Employing reverse-phase and gel permeation high performance liquid chromatography, I was able to obtain several homogeneous peaks of UV absorbance with an apparent selective growth factor activity for cells of the osteoblast phenotype. This novel selective mitogenic activity for osteoblast-like cells was not present in the extracts from all normal and malignant tissue tested other than prostate, and it was absent also from extracts of pre-pubertal prostate. These results demonstrate that the prostate gland contains selective mitogens for osteoblast-like cells, a characteristic which appears to be unique among known mitogens. These mitogens appear furthermore to be androgen dependent. The above data may explain the unique ability of metastatic prostatic cancer to produce blastic reaction in the skeleton. Furthermore the data suggest that products of the normal and abnormal prostate gland may play an important role in skeletal physiology and pathophysiology.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.75368 |
| Date | January 1987 |
| Creators | Koutsilieris, Michael N. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 000419962, proquestno: AAINL38345, Theses scanned by UMI/ProQuest. |
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