Camacho Mercedes, León Xavier, Fernández-Figueras María-Teresa, Quer Miquel, Vila Luis
Laboratory of Angiology, Vascular Biology and Inflammation, Institute of Research, Hospital Santa Creu i Sant Pau, Barcelona, Spain.
Head Neck. 2008 Sep;30(9):1175-81. doi: 10.1002/hed.20850.
Prostaglandin E(2) (PGE(2)) is involved in malignant growth. The objective was to study the PGE(2) pathway in head and neck squamous cell carcinoma (HNSCC) patients.
Expression of cyclooxygenase (COX) and PGE-synthase isoenzymes, and PGE-receptors was determined in biopsies from 83 patients with HNSCC by real-time reverse transcriptase-polymerase chain reaction (RT-PCR).
Expression of COX-2 and cytosolic-PGE-synthase was significantly increased, about 4-fold and 2.5-fold, respectively, in tumors versus paired nontumoral mucosa (n = 34). EP-1 was the only PGE-receptor significantly overexpressed in tumor samples. Expression of COX-1 correlated with mPGES-2 and COX-2 correlated with mPGES-1 (n = 83).
COX-2, functionally coordinated with mPGES-1, is likely to be the limiting enzyme in PGE(2) biosynthesis in HNSCC. The biological meaning of cPGES/p23 overexpression in HNSCC is not yet clear. Our results support the notion that mPGES-1, cPGES, and EP-1 could be the targets for the development of specific PGE(2)-modifier drugs for HNSCC treatment that could avoid negative side effects of COX-2 selective inhibitors.
前列腺素E2(PGE2)参与恶性肿瘤生长。目的是研究头颈部鳞状细胞癌(HNSCC)患者的PGE2通路。
采用实时逆转录聚合酶链反应(RT-PCR)检测83例HNSCC患者活检组织中环氧化酶(COX)、PGE合酶同工酶及PGE受体的表达。
与配对的非肿瘤黏膜相比(n = 34),肿瘤组织中COX-2和胞质型PGE合酶的表达显著增加,分别约为4倍和2.5倍。EP-1是肿瘤样本中唯一显著过表达的PGE受体。COX-1的表达与mPGES-2相关,COX-2的表达与mPGES-1相关(n = 83)。
与mPGES-1功能协同的COX-2可能是HNSCC中PGE2生物合成的限速酶。HNSCC中cPGES/p23过表达的生物学意义尚不清楚。我们的结果支持这样一种观点,即mPGES-1、cPGES和EP-1可能是开发用于HNSCC治疗的特异性PGE2修饰药物的靶点,这类药物可避免COX-2选择性抑制剂的负面副作用。