Petrás Miklós, Hutóczki Gábor, Varga Imre, Vereb György, Szöllosi János, Bognár László, Ruszthi Péter, Kenyeres Annamária, Tóth Judit, Hanzély Zoltán, Scholtz Beáta, Klekner Almos
Debreceni Egyetem Orvos- és Egészségtudományi Centrum Idegsebészeti Klinika, Debrecen.
Magy Onkol. 2009 Sep;53(3):253-8. doi: 10.1556/MOnkol.53.2009.3.3.
Tumor cell invasion into the surrounding brain tissue is mainly responsible for the failure of radical surgical resection and successful treatment, with tumor recurrence as microdisseminated disease. Epidermal growth factor receptors (EGFRs), integrins and their ligands in the extracellular matrix (ECM) predominantly participate in the invasion process, including the cell adhesion to the surrounding microenvironment and cell migration. The extent of infiltration of the surrounding brain tissue by malignant tumors strongly depends on the tumor cell type. Malignant gliomas show much more intensive peritumoral invasion than do metastatic tumors. In this study, the mRNA expression of 29 invasion-related molecules (18 cell membrane receptors or receptor subunits (EGFRs and integrins) and 11 ECM components: collagens, laminins and fibronectin) was investigated by quantitative reverse transcriptase-polymerase chain reaction. Fresh frozen human tissue samples from glioblastoma (GBM) and intracerebral bronchial adenocarcinoma metastases (five pieces from each) were evaluated. Significant differences were established in six of the 29 molecules (ErbB1, 2, 3, integrins alpha3, 7 and beta1). To confirm our results at the protein level, immunohistochemical analysis of nine molecules was performed. The staining intensity differed definitely in the case of ErbB1, 2 and integrins alpha3 and beta1. Determining the differences in invasion-related molecules in tumors of different origin can help identify the exact molecular mechanisms that facilitate peritumoral infiltration by glioblastoma cells. These results should allow the selection of target molecules for potential chemotherapeutic agents directed against highly invasive malignant gliomas.
肿瘤细胞侵入周围脑组织是根治性手术切除失败和治疗成功的主要原因,肿瘤复发表现为微小播散性疾病。表皮生长因子受体(EGFRs)、整合素及其在细胞外基质(ECM)中的配体主要参与侵袭过程,包括细胞与周围微环境的黏附及细胞迁移。恶性肿瘤对周围脑组织的浸润程度很大程度上取决于肿瘤细胞类型。恶性胶质瘤的瘤周浸润比转移性肿瘤更为强烈。在本研究中,通过定量逆转录-聚合酶链反应研究了29种侵袭相关分子(18种细胞膜受体或受体亚基(EGFRs和整合素)以及11种ECM成分:胶原蛋白、层粘连蛋白和纤连蛋白)的mRNA表达。评估了来自胶质母细胞瘤(GBM)和脑内支气管腺癌转移灶的新鲜冷冻人体组织样本(各5份)。在29种分子中的6种(ErbB1、2、3、整合素α3、7和β1)中发现了显著差异。为了在蛋白质水平上证实我们的结果,对9种分子进行了免疫组织化学分析。在ErbB1、2以及整合素α3和β1的情况下,染色强度肯定不同。确定不同起源肿瘤中侵袭相关分子的差异有助于识别促进胶质母细胞瘤细胞瘤周浸润的确切分子机制。这些结果应有助于选择针对高侵袭性恶性胶质瘤的潜在化疗药物的靶分子。