Medizinische Universitätsklinik, Knappschaftskrankenhaus, IMBL, Ruhr-Universität Bochum, Bochum, Germany.
Life Sci. 2011 Aug 29;89(9-10):304-12. doi: 10.1016/j.lfs.2011.06.020. Epub 2011 Jul 6.
Members of the epidermal growth factor receptor (EGFR) family represent validated targets for anti-cancer therapy and EGFR inhibitors have also shown efficacy in pancreatic carcinoma. We here described in detail molecular forms of the EGF receptor released by pancreatic cancer cells. We found peptides specific for the EGFR in the secretomes of five pancreatic cancer cell lines. Secretomes from cultured cancer cells are widely used as sources for serum biomarker discovery.
The detailed analysis of EGFR forms in secretomes of human pancreatic cancer cells is a compilation of results from mass spectrometry (MS) and Western blotting with intracellular and extracellular domain specific antibodies.
Pancreatic cancer cells secrete a 110 kDa soluble form of the EGFR (sEGFR) representing the ligand binding extracellular EGFR domains and presumably released by ectodomain shedding. At the same time, as constituents of exosomes, the EGFR is released as full-length intact receptor (170 kDa) and as a 65 kDa processed form, the C-terminal remnant fragment that corresponds to the intracellular kinase domain.
The detailed characterization of diverse EGFR forms released by pancreatic cancer cells in vitro and presumably in vivo bears important implications for functional studies, for the validation of soluble EGFR as a serum biomarker and for the design of targeted therapies.
表皮生长因子受体（EGFR）家族成员是癌症治疗的有效靶点，EGFR 抑制剂在胰腺癌中也显示出疗效。我们在这里详细描述了由胰腺癌细胞释放的 EGFR 分子形式。我们在 5 种胰腺癌细胞系的分泌组中发现了针对 EGFR 的肽。培养的癌细胞分泌组被广泛用作血清生物标志物发现的来源。
人胰腺癌细胞分泌组中 EGFR 形式的详细分析是质谱（MS）和用细胞内和细胞外结构域特异性抗体进行 Western blot 分析结果的综合。
胰腺癌细胞分泌一种 110 kDa 的可溶性 EGFR（sEGFR），代表配体结合的 EGFR 细胞外结构域，推测通过外切酶脱落释放。同时，作为外泌体的组成部分，EGFR 作为全长完整受体（170 kDa）和 65 kDa 的加工形式释放，即与细胞内激酶结构域相对应的 C 端残片。
详细描述胰腺癌细胞在体外和体内释放的不同 EGFR 形式，对功能研究、验证可溶性 EGFR 作为血清生物标志物以及设计靶向治疗具有重要意义。
