Kuniyasu Hiroki, Chihara Yoshitomo, Kondo Hideaki, Ohmori Hitoshi, Ukai Rinzo
Department of Oncological Pathology, Cancer Center, Nara Medical University, Nara 734-8521, Japan.
Oncol Rep. 2003 Nov-Dec;10(6):1863-8.
Amphoterin, the major product of the high mobility group-1 gene, is a ligand associated with cancer invasion and metastasis through activation of the receptor for advanced glycation end products (RAGE). Expression of amphoterin and RAGE was examined in prostatectomy specimens from 40 patients with pT3 prostate cancer (18 non-metastatic and 22 metastatic) preoperatively treated with lutenizing hormone-releasing hormone (LH-RH) agonist. Amphoterin expression was detected in tumor cells of 6 (27%) metastatic and 0 non-metastatic cases (p<0.0001). Amphoterin was also detected in prostatic stromal cells of 14 (63%) metastatic cases and 2 (11%) non-metastatic cases (p=0.0010). RAGE production was detected in cancer cells of 16 (73%) metastatic and 6 (33%) non-metastatic cases (p=0.0244). A total of 2 (22%) non-metastatic and 16 (73%) metastatic cases showed co-expression of amphoterin and RAGE in tumor cells or in tumor cells and stromal cells (p=0.0001). The in vitro invasive capacity of PC-3, a prostatic cancer cell line that co-expressed amphoterin and RAGE, was suppressed by treatment with amphoterin antisense S-oligodeoxynucleotide (ODN). Primary cultured human prostatic stromal cells secreted no amphoterin; however, amphoterin secretion was induced by androgen deprivation. The conditioned medium of human prostatic stromal cells deprived of androgen recovered the in vitro invasive capacity of PC-3 cells suppressed by amphoterin antisense S-ODN. These results suggest that androgen deprivation provides a paracrine interaction between cancer and stromal cells through the RAGE-amphoterin system in advanced prostate cancer.
高迁移率族蛋白1基因的主要产物两性调节蛋白是一种通过激活晚期糖基化终末产物受体（RAGE）而与癌症侵袭和转移相关的配体。在40例术前接受促黄体激素释放激素（LH-RH）激动剂治疗的pT3期前列腺癌患者（18例无转移和22例有转移）的前列腺切除标本中检测了两性调节蛋白和RAGE的表达。在6例（27%）有转移病例的肿瘤细胞中检测到两性调节蛋白表达，而无转移病例中未检测到（p<0.0001）。在14例（63%）有转移病例和2例（11%）无转移病例的前列腺基质细胞中也检测到两性调节蛋白（p=0.0010）。在16例（73%）有转移病例和6例（33%）无转移病例的癌细胞中检测到RAGE产生（p=0.0244）。共有2例（22%）无转移病例和16例（73%）有转移病例在肿瘤细胞或肿瘤细胞与基质细胞中显示两性调节蛋白和RAGE共表达（p=0.0001）。同时表达两性调节蛋白和RAGE的前列腺癌细胞系PC-3的体外侵袭能力通过两性调节蛋白反义硫代寡脱氧核苷酸（ODN）处理而受到抑制。原代培养的人前列腺基质细胞不分泌两性调节蛋白；然而，雄激素剥夺可诱导两性调节蛋白分泌。雄激素剥夺的人前列腺基质细胞的条件培养基恢复了被两性调节蛋白反义硫代ODN抑制的PC-3细胞的体外侵袭能力。这些结果表明，在晚期前列腺癌中，雄激素剥夺通过RAGE-两性调节蛋白系统在癌细胞和基质细胞之间提供了旁分泌相互作用。
