An orthotopic model for the study of growth factors in the ventral prostate of the rat: effects of epidermal growth factor and basic fibroblast growth factor.

Abstract

In order to determine if epidermal growth factor (EGF) or basic fibroblast growth factor (bFGF) are capable of stimulating prostatic growth in situ, we complexed EGF and bFGF to a Matrigel (MG) vehicle that was subsequently injected orthotopically into the ventral prostate of adult rats. Three weeks following a single injection of 0.1 ng of EGF or bFGF, the wet weight of the growth factor-injected lobes of the ventral prostate was increased (P < or = 0.025) 144 +/- 14% and 138 +/- 8%, respectively compared to contralateral lobes injected with MG only. Total DNA and protein per lobe (P < or = 0.025) and the incorporation of bromodeoxyuridini (BrdUrd; P < or 0.01) were all significantly increased in lobes injected with EGF or bFGF compared to MG-injected lobes. Thus, EGF and bFGF were stimulating true growth of the rat ventral prostate in situ. The induced prostatic growth was ligand specific, because co-injection with neutralizing antibodies abolished EGF and bFGF stimulation of prostatic wet weight. The effect of a single injection of 0.1 ng of growth factor was long-lasting and elevated prostatic wet weight for 4 (P < or = 0.05; bFGF) to 6 (P < or = 0.05; EGF) weeks. Histologic evaluation did not reveal any gross changes in the ratio of stroma to epithelium in either EGF- or bFGF-injected lobes at the 0.1 ng/lobe dose. A slight hyperplasia of the prostatic epithelium was detected in lobes injected with 10 ng of EGF. Of note, the incorporation of BrdUrd was primarily localized in the luminal and basal epithelial cells, whereas incorporation into the prostatic stroma was scanty in lobes injected with either EGF or bFGF. In summary, we have developed an orthotopic model enabling the study of the roles of growth factors in prostatic physiology, function, and disease in situ. Additionally, we have demonstrated that when injected orthotopically into the rat ventral prostate, EGF and bFGF stimulate the growth of the prostatic epithelium to similar degrees.