Sellers Rani S, LeRoy Bruce E, Blomme Eric A G, Tannehill-Gregg Sarah, Corn Stephanie, Rosol Thomas J
The Department of Veterinary Biosciences, The Ohio State University, Columbus, 43210, USA.
Prostate. 2004 Mar 1;58(4):366-73. doi: 10.1002/pros.20029.
Bone metastases of prostate carcinoma are associated with osteoblastic metastases. Tumor-derived factors, such as parathyroid hormone-related protein (PTHrP), may promote the development of osteoblastic metastases. We examined the effect of transforming growth factor-beta1 (TGF beta 1) on PTHrP mRNA expression and PTHrP secretion in normal canine prostate epithelial cells (PEC) and stromal cells (PSC), and in canine prostate carcinoma cells (PCC).
Primary cultures of PEC, PSC, and PCC were produced. The effect of TGF beta 1 on PTHrP mRNA expression was measured by Northern blot, and secretion of PTHrP into culture medium was measured by immunoradiometric assay (IRMA). Degradation of recombinant-human PTHrP (rhPTHrP) (1-84) inoculated in prostate cell cultures was measured over 24 hr. Arginine esterase (AE) activity in tissue and conditioned medium was also measured.
TGF beta 1 increased PTHrP mRNA expression in a time- and dose-dependent manner in PEC and in PCC. TGF beta 1 decreased PTHrP mRNA in PSC. TGF beta 1 significantly increased PTHrP secretion (P < or = 0.05) into PEC but not PSC conditioned medium. rhPTHrP was significantly (P < or = 0.05) degraded in PEC conditioned medium as compared to PSC conditioned medium. AE activity was present in prostate and prostate carcinoma tissue, but not in conditioned medium from PEC or PSC.
TGF beta 1 increased PTHrP mRNA expression in canine PEC and PCC, and decreased expression in PSC. This regulatory pathway may be important in the pathogenesis of osteoblastic metastases.
前列腺癌的骨转移与成骨细胞转移有关。肿瘤衍生因子，如甲状旁腺激素相关蛋白（PTHrP），可能促进成骨细胞转移的发展。我们研究了转化生长因子-β1（TGFβ1）对正常犬前列腺上皮细胞（PEC）、基质细胞（PSC）以及犬前列腺癌细胞（PCC）中PTHrP mRNA表达和PTHrP分泌的影响。
制备PEC、PSC和PCC的原代培养物。通过Northern印迹法检测TGFβ1对PTHrP mRNA表达的影响，通过免疫放射分析（IRMA）检测PTHrP分泌到培养基中的情况。在24小时内检测接种于前列腺细胞培养物中的重组人PTHrP（rhPTHrP）（1-84）的降解情况。还检测了组织和条件培养基中的精氨酸酯酶（AE）活性。
TGFβ1在PEC和PCC中以时间和剂量依赖性方式增加PTHrP mRNA表达。TGFβ1降低PSC中的PTHrP mRNA。TGFβ1显著增加PEC条件培养基中PTHrP的分泌（P≤0.05），但对PSC条件培养基无此作用。与PSC条件培养基相比，rhPTHrP在PEC条件培养基中显著（P≤0.05）降解。前列腺和前列腺癌组织中存在AE活性，但PEC或PSC的条件培养基中未检测到。
TGFβ1增加犬PEC和PCC中PTHrP mRNA表达，降低PSC中的表达。该调节途径在成骨细胞转移的发病机制中可能很重要。
