Streit M, Schmidt R, Hilgenfeld R U, Thiel E, Kreuser E D
Department of Hematology and Oncology, University Medical Center Benjamin Franklin, Free University, Berlin, Germany.
J Mol Med (Berl). 1996 May;74(5):253-68. doi: 10.1007/BF00196578.
Changes in the expression and function of adhesion molecules on the surface of cancer cells are important characteristics in the development of gastrointestinal malignancies and might be used in the future as prognostic factors or as new targets for diagnostic and therapeutic approaches. In esophageal cancer a down-regulation of the E-cadherin receptor and the cytoplasmic protein alpha-catenin is associated with tumor dedifferentiation, infiltrative growth and lymph-node metastasis. In gastric cancer a reduction of E-cadherin expression due to gene mutations is restricted to diffuse-type tumors while the occurrence of the CD44-standard and the CD44-9v isoform is significantly related to a higher tumor-induced mortality and a shorter survival time. The CD44-6v isoform is predominantly expressed by intestinal-type gastric carcinomas, giving these tumor cells the ability to perform lymph-node metastasis. In pancreatic cancer the expression of integrin adhesion receptors is significantly altered during the malignant transformation while a loss of the E-cadherin receptor can generate dedifferentiation and invasiveness of pancreas carcinoma cells. There is increasing evidence that integrin receptors as well as different isoforms of the CD44 receptor are altered following the malignant transformation of colonic mucosa into adenomas and invasive carcinomas. The expression of the CD44-6v isoform seems to be associated with an adverse prognosis in colorectal cancer due to the development of tumor metastases. A strong correlation has been observed between the expression of the 67-kDa laminin receptor and the degree of differentiation, the invasive phenotype and the metastatic abilities af colorectal cancer cells. Analyzing the expression of the E-cadherin receptor showed that this receptor may serve as an independent prognostic marker in Dukes' stage B colorectal cancer to identify patients with poor prognosis and designate them for intensive adjuvant therapy and clinical observation after curative surgical tumor treatment.
癌细胞表面黏附分子表达和功能的变化是胃肠道恶性肿瘤发生发展的重要特征，未来可能用作预后因素或作为诊断和治疗方法的新靶点。在食管癌中，E-钙黏蛋白受体和细胞质蛋白α-连环蛋白的下调与肿瘤去分化、浸润性生长及淋巴结转移相关。在胃癌中，由于基因突变导致的E-钙黏蛋白表达降低仅限于弥漫型肿瘤，而CD44标准型和CD44-9v异构体的出现与较高的肿瘤诱导死亡率及较短的生存时间显著相关。CD44-6v异构体主要由肠型胃癌表达，赋予这些肿瘤细胞进行淋巴结转移的能力。在胰腺癌中，整合素黏附受体的表达在恶性转化过程中显著改变，而E-钙黏蛋白受体的缺失可导致胰腺癌细胞去分化和侵袭性增强。越来越多的证据表明，整合素受体以及CD44受体的不同异构体在结肠黏膜恶性转化为腺瘤和浸润性癌后会发生改变。由于肿瘤转移的发生，CD44-6v异构体的表达似乎与结直肠癌的不良预后相关。已观察到67-kDa层粘连蛋白受体的表达与结直肠癌细胞的分化程度、侵袭表型及转移能力之间存在密切相关性。分析E-钙黏蛋白受体的表达表明，该受体可作为Dukes B期结直肠癌的独立预后标志物，以识别预后不良的患者，并在根治性手术肿瘤治疗后将其指定为强化辅助治疗和临床观察对象。
