Scavo Maria Principia, Fucci Livia, Caldarola Lucia, Mangia Anita, Azzariti Amalia, Simone Giovanni, Gasparini Giampietro, Krol Silke
Translational Nanotechnology Laboratory, IRCCS Istituto Tumori "Giovanni Paolo II", 70124 Bari, Italy.
Pathology Laboratory, IRCCS Istituto Tumori "Giovanni Paolo II", 70124 Bari, Italy.
Oncotarget. 2017 Dec 12;9(1):824-830. doi: 10.18632/oncotarget.23159. eCollection 2018 Jan 2.
Frizzled (FZD) proteins, a family of Wnt receptors, are involved in carcinogenesis in different organs. One interesting FZD protein is FZD-10 highly expressed in embryogenesis but completely absent in the membrane or cytosol of healthy proliferated cells. We studied in detail the expression level and the location of Frizzled-10 protein in different cancerous tissues, such as colon, melanoma and gastric cancer and in function of different staging of the tumor and in metastases. We observed a correlation between cancer evolution and FZD-10 expression, and localization of protein during carcinogenesis. In colon, we have an increase of cytoplasmic FZD-10 expression from hyperplastic mucosa to metastatic tissues, while the amount in the nucleus decreases significantly in T3 and T4 staging tumors as well as in metastases. In melanoma and gastric cancer, we observed the opposite trend of FZD-10 protein in the cytosol but both show a decrease in the T3 and T4 stage of the tumor and in metastases. However, the decrease is less prominent in gastric cancer. Our findings indicate an important role of FZD-10 in tumor progression especially in the later stages of tumor. The nuclear expression of FZD-10 or its absence can give a new tool for tumor staging to pathologists. For target therapy, at least for colon cancer, the high presence of FZD-10 in the later stages of tumor progression and the absence in healthy tissue present a promising new approach.
卷曲蛋白(FZD)家族作为Wnt受体,参与不同器官的致癌过程。一种有趣的FZD蛋白是FZD - 10,它在胚胎发育中高度表达,但在健康增殖细胞的细胞膜或细胞质中完全不存在。我们详细研究了卷曲蛋白 - 10在不同癌组织(如结肠癌、黑色素瘤和胃癌)中的表达水平和定位,以及其与肿瘤不同分期和转移的关系。我们观察到癌症进展与FZD - 10表达以及致癌过程中蛋白定位之间存在相关性。在结肠癌中,从增生性黏膜到转移组织,细胞质中FZD - 10的表达增加,而在T3和T4期肿瘤以及转移灶中,细胞核中的含量显著降低。在黑色素瘤和胃癌中,我们观察到细胞质中FZD - 10蛋白呈现相反的趋势,但在肿瘤的T3和T4期以及转移灶中均显示下降。然而,这种下降在胃癌中不太明显。我们的研究结果表明FZD - 10在肿瘤进展中尤其是在肿瘤后期发挥重要作用。FZD - 10的核表达或其缺失可为病理学家提供一种新的肿瘤分期工具。对于靶向治疗,至少对于结肠癌而言,FZD - 10在肿瘤进展后期的高表达以及在健康组织中的缺失提供了一种有前景的新方法。