Department of Orthopedic Surgery, Wake Forest University School of Medicine, 1 Medical Center Boulevard, Winston-Salem, NC 27101, USA.
Department of Radiation Oncology, Wake Forest University School of Medicine, 1 Medical Center Boulevard, Winston-Salem, NC 27101, USA.
Int J Mol Sci. 2024 May 30;25(11):6014. doi: 10.3390/ijms25116014.
Osteoarthritis (OA) is increasing worldwide, and previous work found that OA increases systemic cartilage oligomeric matrix protein (COMP), which has also been implicated in prostate cancer (PCa). As such, we sought to investigate whether OA augments PCa progression. Cellular proliferation and migration of RM1 murine PCa cells treated with interleukin (IL)-1α, COMP, IL-1α + COMP, or conditioned media from cartilage explants treated with IL-1α (representing OA media) and with inhibitors of COMP were assessed. A validated murine model was used for tumor growth and marker expression analysis. Both proliferation and migration were greater in PCa cells treated with OA media compared to controls ( < 0.001), which was not seen with direct application of the stimulants. Migration and proliferation were not negatively affected when OA media was mixed with downstream and COMP inhibitors compared to controls ( > 0.05 for all). Mice with OA developed tumors 100% of the time, whereas mice without OA only 83.4% ( = 0.478). Tumor weight correlated with OA severity (Pearson correlation = 0.813, = 0.002). Moreover, tumors from mice with OA demonstrated increased Ki-67 expression compared to controls (mean 24.56% vs. 6.91%, = 0.004) but no difference in CD31, PSMA, or COMP expression ( > 0.05). OA appears to promote prostate cancer in vitro and in vivo.
骨关节炎（OA）在全球范围内呈上升趋势，先前的研究发现 OA 会增加系统性软骨寡聚基质蛋白（COMP），而 COMP 也与前列腺癌（PCa）有关。因此，我们试图研究 OA 是否会加剧 PCa 的进展。用白细胞介素（IL）-1α、COMP、IL-1α+COMP 或经 IL-1α 处理的软骨外植体的条件培养基（代表 OA 培养基）处理 RM1 鼠前列腺癌细胞，评估细胞增殖和迁移。使用经过验证的鼠模型进行肿瘤生长和标志物表达分析。与对照组相比，用 OA 培养基处理的 PCa 细胞的增殖和迁移都更大（<0.001），而直接应用刺激物则没有这种情况。与对照组相比，当 OA 培养基与下游和 COMP 抑制剂混合时，迁移和增殖并没有受到负面影响（>0.05）。患有 OA 的小鼠 100%出现肿瘤，而没有 OA 的小鼠只有 83.4%（=0.478）。肿瘤重量与 OA 严重程度相关（Pearson 相关系数=0.813，=0.002）。此外，与对照组相比，患有 OA 的小鼠的肿瘤中 Ki-67 表达增加（平均值 24.56%对 6.91%，=0.004），但 CD31、PSMA 或 COMP 表达没有差异（>0.05）。OA 似乎在体外和体内促进前列腺癌的发展。
