Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, USA.
Department of Otolaryngology, Meir Hospital, Kfar Saba, Israel.
Sci Rep. 2020 Mar 6;10(1):4227. doi: 10.1038/s41598-020-60675-2.
Laryngeal squamous cell carcinoma (LSCC) responds to 17β-estradiol via estrogen-receptor (ER, transcribed from ESR1) dependent mechanisms, but is not recognized as a hormonally responsive cancer. 17β-estradiol production by LSCC cell lines UM-SCC-11A and UM-SCC-12 was examined. Wild type (WT) and ESR1-silenced LSCC cultures and xenografts were examined for 17β-estradiol responsiveness in vivo. 14 LSCC and surrounding epithelial samples at various pathological stages were obtained from patients; ERα and ERβ expression were verified using data from the total cancer genome atlas. UM-SCC-11A and UM-SCC-12 both produce 17β-estradiol, but only UM-SCC-12, not UM-SCC-11A, xenograft tumors grow larger in vivo in response to systemic 17β-estradiol treatments. ERα66 and ERα36 expression inversely correlated with clinical cancer stage and tumor burden. LSCC ERα66 expression was higher compared to surrounding epithelia in indolent samples but lower in aggressive LSCC. ERβ expression was highly variable. High ESR1 expression correlated with improved survival in LSCC. Loss of ERα66 expression inversely correlated with prognosis in LSCC. ERα66 may be a histopathological marker of aggression in LSCC.
喉鳞状细胞癌 (LSCC) 通过雌激素受体 (ER，转录自 ESR1) 依赖的机制对 17β-雌二醇产生反应，但不被认为是一种激素反应性癌症。检查了 LSCC 细胞系 UM-SCC-11A 和 UM-SCC-12 中 17β-雌二醇的产生。检查了野生型 (WT) 和 ESR1 沉默的 LSCC 培养物和异种移植物在体内对 17β-雌二醇的反应性。从患者获得了 14 个处于不同病理阶段的 LSCC 和周围上皮样本；使用来自全癌症基因组图谱的数据验证了 ERα 和 ERβ 的表达。UM-SCC-11A 和 UM-SCC-12 均可产生 17β-雌二醇，但只有 UM-SCC-12 而不是 UM-SCC-11A 的异种移植肿瘤在体内对全身 17β-雌二醇治疗的反应中生长更大。ERα66 和 ERα36 的表达与临床癌症分期和肿瘤负担呈负相关。LSCC ERα66 的表达与惰性样本中周围上皮相比更高，但在侵袭性 LSCC 中更低。ERβ 的表达高度可变。ESR1 高表达与 LSCC 患者的生存改善相关。ERα66 表达缺失与 LSCC 的预后呈负相关。ERα66 可能是 LSCC 侵袭性的组织病理学标志物。
