α-Parvin, a pseudopodial constituent, promotes cell motility and is associated with lymph node metastasis of lobular breast carcinoma
α-Parvin, a pseudopodial constituent, promotes cell motility and is associated with lymph node metastasis of lobular breast carcinoma
复制标题
DOI：
10.1007/s10549-014-2859-0
复制
发表时间：
2014-02-01
影响因子：
3.8
通讯作者：
Ito, Akihiko
中科院分区：
文献类型：
--
作者：
Ito, Masaoki;Hagiyama, Man;Ito, Akihiko
浸润性小叶癌(ILC)较浸润性导管癌(IDC)淋巴结阳性率高，且ILC细胞浸润具有明显的组织学特征，提示ILC特异性侵袭分子的作用。为了确定这样的分子，我们使用了蛋白质组学方法在MDA-MB-231乳腺癌细胞的伪足中。用准分子激光消融、双向差示凝胶电泳法、质谱仪和免疫细胞荧光法鉴定了伪足成分。通过瞬时转染法修饰MDA-MB-231细胞以表达不同水平的该成分，并通过伤口愈合和双室实验检测伪足的形成和迁移能力。对56例ILC和21例IDC进行免疫组织化学染色，并与临床病理指标进行比较。一种肌动蛋白结合接头蛋白，α-Parvin，被发现定位于伪足，并在没有被诱导延伸伪足的细胞中形成局灶性粘连。伪足的长度、密度和迁移能力与α-Parvin的表达相关。21例(37.5%)ILCα-Parvin阳性，而所有21例IDC均为阴性(P<；0.001)。在单因素分析中，α-Parvin阳性表达与淋巴侵袭(P=0.038)和淋巴结转移(P=0.003)显著相关，在多因素分析中与淋巴结转移(P=0.020)显著相关。α-Parvin是一种伪足成分，可促进乳腺癌细胞的迁移，并由ILC专一表达，提示α-Parvin是一种ILC特异的侵袭分子，可作为ILC侵袭性亚群的临床标志物。
Invasive lobular carcinoma (ILC) is more frequently lymph node positive than is invasive ductal carcinoma (IDC), and ILC cell infiltration shows distinctive histological characteristics, suggesting the action of ILC-specific invasion molecules. To identify such a molecule, we used a proteomic approach in the pseudopodia of MDA-MB-231 breast cancer cells. A pseudopodial constituent was identified using excimer laser ablation, two-dimensional difference gel electrophoresis, mass spectroscopy, and immunocytofluorescence. MDA-MB-231 cells were modified to express various levels of this constituent by transient transfection and were examined for pseudopodia formation and migratory abilities using wound healing and two-chamber assays. Immunohistochemical positivity of human breast cancer cells (56 ILCs and 21 IDCs) was compared with clinicopathological variables. An actin-binding adaptor protein, alpha-parvin, was found to localize to pseudopodia and to form focal adhesions in cells not induced to extend pseudopodia. Pseudopodial length and density and migratory abilities correlated with alpha-parvin expression. Twenty-one (37.5 %) ILCs stained positive for alpha-parvin, whereas the results were negative for all 21 IDCs (P < 0.001). alpha-Parvin positivity in ILC was significantly associated with lymphatic invasion (P = 0.038) and lymph node metastasis (P = 0.003) in univariate analyses and to lymph node metastasis (P = 0.020) in multivariate analyses. alpha-Parvin, a pseudopodial constituent, was found to promote migration of breast cancer cells and to be expressed exclusively by ILC, suggesting that alpha-parvin is an ILC-specific invasion molecule that may have clinical utility as a biomarker for aggressive subsets of ILC.