Gladson C L, Hancock S, Arnold M M, Faye-Petersen O M, Castleberry R P, Kelly D R
Department of Pathology, University of Alabama at Birmingham 35294-0007, USA.
Am J Pathol. 1996 May;148(5):1423-34.
The ligand specificity of the integrin cell adhesion receptors probably determines the ability of specific integrins to promote tumor cell proliferation and metastasis. Therefore, we compared the expression of integrin alphaVbeta3, a promiscuous receptor that binds with high affinity to numerous cell matrix proteins, with the expression of integrin alphaVbeta5 and the integrin beta 1 subunit (which pairs with multiple alpha subunits) in neuroblastic tumors at various stages of differentiation. Undifferentiated neuroblastoma tumors rapidly invade and metastasize, whereas ganglioneuroblastomas rarely metastasize. Differentiating neuroblastomas are associated with an intermediate prognosis. Paraffin sections of neuroblastic tumors at various stages of differentiation obtained at biopsy from 17 patients were hybridized with antisense integrin subunit-specific alphaV, beta3, beta1, and beta5 riboprobes. All neuroblastic tumors and seven adrenal glands obtained at autopsy were analyzed immunohistochemically with antibodies directed toward the alphaV, beta3, beta1, and beta5 subunits. The alphaV subunit was expressed in neuroblastic tumors independent of the stage of differentiation, although mRNA and protein expression were generally weak in ganglioneuroblastomas, and was also detected in adrenal gland medullae. The beta1 subunit was detected in most neuroblastic tumors independent of the stage of differentiation as well as in adrenal gland medullae. In contrast, the beta3 subunit, which was not expressed in adrenal gland medullae, was expressed at the protein and mRNA levels in undifferentiated neuroblastomas (six of seven and seven of seven, respectively) but was not expressed in neuroblasts or ganglion cells in ganglioneuroblastomas (one case weakly positive out of five). The beta 5 subunit was expressed at the protein (five of five) and mRNA (four of five) levels in the ganglion cells of ganglioneuroblastomas and, although mRNA for this subunit was detectable in undifferentiated tumors, the protein was not detectable. The expression of integrin alphaVbeta3 in undifferentiated neuroblastomas may contribute to the rapid growth of these tumors and their tendency to metastasize.
整合素细胞黏附受体的配体特异性可能决定了特定整合素促进肿瘤细胞增殖和转移的能力。因此，我们比较了整合素αVβ3（一种能与多种细胞基质蛋白高亲和力结合的多配体受体）与整合素αVβ5以及整合素β1亚基（可与多种α亚基配对）在不同分化阶段的神经母细胞瘤中的表达情况。未分化的神经母细胞瘤肿瘤迅速侵袭和转移，而神经节神经母细胞瘤很少转移。正在分化的神经母细胞瘤预后中等。从17例患者活检获得的不同分化阶段的神经母细胞瘤石蜡切片，与整合素亚基特异性αV、β3、β1和β5反义核糖探针进行杂交。对所有神经母细胞瘤以及7个尸检获得的肾上腺进行免疫组织化学分析，使用针对αV、β3、β1和β5亚基的抗体。αV亚基在神经母细胞瘤中表达，与分化阶段无关，尽管在神经节神经母细胞瘤中mRNA和蛋白表达通常较弱，并且在肾上腺髓质中也可检测到。β1亚基在大多数神经母细胞瘤中均可检测到，与分化阶段无关，在肾上腺髓质中也有表达。相比之下，β3亚基在肾上腺髓质中不表达，在未分化的神经母细胞瘤中蛋白和mRNA水平均有表达（分别为7例中的6例和7例中的7例），但在神经节神经母细胞瘤的神经母细胞或神经节细胞中不表达（5例中有1例弱阳性）。β5亚基在神经节神经母细胞瘤的神经节细胞中蛋白（5例中的5例）和mRNA（5例中的4例）水平均有表达，尽管在未分化肿瘤中可检测到该亚基的mRNA，但蛋白未检测到。未分化神经母细胞瘤中整合素αVβ3的表达可能有助于这些肿瘤的快速生长及其转移倾向。
