Pham K, Milovanovic T, Barr R J, Truong T, Holcombe R F
Division of Hematology/Oncology and Chao Family Comprehensive Cancer Center, University of California, Irvine, CA 92868, USA.
Mol Pathol. 2003 Oct;56(5):280-5. doi: 10.1136/mp.56.5.280.
Secreted Wnt ligands are key proteins regulating cell-cell interactions and cell growth and differentiation. These proteins, along with other components of the Wnt signalling pathway, are involved in the malignant transformation of various human cancers, including malignant melanoma. This study defines the expression of several members of the Wnt ligand family and correlates their expression with histological characteristics.
The expression of Wnt2, Wnt5a, Wnt5b, Wnt7b, and Wnt10b was defined by in situ, antisense RNA hybridisation of paraffin wax embedded sections of benign naevi and malignant melanoma. Immunoperoxidase based antibody staining was used to define the expression of frizzled (Fz) receptors.
All naevi tested strongly expressed Wnt2, Wnt5a, Wnt7b, and Wnt10b. Melanomas characterised by small, uniform cells expressed each of the Wnts in a pattern similar to that seen for benign naevi. In contrast, melanomas characterised by large, pleomorphic cells expressed Wnt10b but did not express Wnt2 and had low levels of expression of Wnt5a. Expression of Wnt7b was variable in these melanomas. Fz receptor expression was present at a low level in normal epithelium and all naevi and melanomas.
The expression pattern of Wnt ligands in malignant melanoma correlates with histopathological features and may provide a basis for the molecular classification of this disease.
分泌型Wnt配体是调节细胞间相互作用以及细胞生长和分化的关键蛋白。这些蛋白与Wnt信号通路的其他组分一起，参与包括恶性黑色素瘤在内的多种人类癌症的恶性转化。本研究确定了Wnt配体家族几个成员的表达情况，并将它们的表达与组织学特征相关联。
通过对良性痣和恶性黑色素瘤石蜡包埋切片进行原位反义RNA杂交，确定Wnt2、Wnt5a、Wnt5b、Wnt7b和Wnt10b的表达。采用基于免疫过氧化物酶的抗体染色来确定卷曲蛋白（Fz）受体的表达。
所有检测的痣均强烈表达Wnt2、Wnt5a、Wnt7b和Wnt10b。以小的、形态一致的细胞为特征的黑色素瘤，其每种Wnt的表达模式与良性痣相似。相比之下，以大的、多形性细胞为特征的黑色素瘤表达Wnt10b，但不表达Wnt2，且Wnt5a表达水平较低。在这些黑色素瘤中，Wnt7b的表达存在差异。Fz受体在正常上皮以及所有痣和黑色素瘤中均低水平表达。
恶性黑色素瘤中Wnt配体的表达模式与组织病理学特征相关，可能为该疾病的分子分类提供依据。
