INTEGRIN EXPRESSION IN HUMAN NEUROBLASTOMA-CELLS WITH OR WITHOUT N-MYC AMPLIFICATION AND IN ECTOPIC/ORTHOTOPIC NUDE-MOUSE TUMORS
INTEGRIN EXPRESSION IN HUMAN NEUROBLASTOMA-CELLS WITH OR WITHOUT N-MYC AMPLIFICATION AND IN ECTOPIC/ORTHOTOPIC NUDE-MOUSE TUMORS
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DOI：
10.1006/excr.1994.1185
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发表时间：
1994-07-01
影响因子：
3.7
通讯作者：
CULP, LA
中科院分区：
文献类型：
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作者：
FLICKINGER, KS;JUDWARE, R;CULP, LA
三个人神经母细胞瘤细胞系，有或没有N-myc扩增，评价其整合素的表达模式作为培养细胞，以及其裸鼠皮下（异位）或肾上腺（原位）注射后获得的肿瘤。IMR-32和LaN 1细胞（具有扩增的N-myc）不表达任何识别纤连蛋白或胶原的常见整合素亚基，如通过用特异性单克隆抗体免疫沉淀细胞提取物所确定的;同样适用于IMR-32或LaN 1的所有皮下或肾上腺肿瘤，表明它们在任一部位的原发性肿瘤形成期间不是必需的。SK-N-SH细胞（具有二倍体N-myc）表达预期大小的β 1、α 2和α 3亚基（α 2在145 kDa处未裂解），但不表达α 1、α 4、α 5、α V或β 3。这种表达模式在所有第一轮皮下和肾上腺肿瘤细胞群中以及在源自第一轮皮下肿瘤的第二轮皮下肿瘤中是保守的（没有肿瘤表达β 3）。一个显着的差异，指出皮下和肾上腺肿瘤人群：所有的第一轮和第二轮皮下肿瘤表达高水平的α V亚基，而肾上腺肿瘤不表达任何α V。这一结果表明，在皮下原发性肿瘤形成的α V β 1的一些基本功能。还通过荧光激活细胞分选评价整合素模式。SK-N-SH及其衍生肿瘤在细胞表面表达不均匀量的β 1和α 2，而只有皮下肿瘤细胞表达α V。亲代SK-N-SH细胞包含两个亚群，其中一半表达α 3，而另一半不表达;所有的皮下肿瘤细胞都保持了这种两个亚群的模式，这表明原发性肿瘤的形成不会导致较大原发性肿瘤中α 3（-）或α 3（+）细胞类型的克隆优势。虽然这些结果表明神经母细胞瘤中N-myc扩增和整联蛋白表达下调之间存在相关性，但它们证明了在小鼠模型系统中异位或原位位点的两轮原发性肿瘤形成期间整联蛋白表达的保守性，皮下位点α V β 1表达的诱导和/或选择，以及在整个原发性肿瘤发展过程中α 3 β 1表达的克隆异质性。(C)1994年出版社出版。
Three human neuroblastoma cell lines, with or without N-myc amplification, were evaluated for their integrin expression patterns as cultured cells, as well as their nude mouse-borne tumors obtained after subcutaneous (ectopic) or adrenal gland (orthotopic) injection. IMR-32 and LaN1 cells (with amplified N-myc) do not express any of the common integrin subunits that recognize fibronectin or collagens, as determined by immunoprecipitation of cell extracts with specific monoclonal antibodies; the same was true for all subcutaneous or adrenal tumors from IMR-32 or LaN1, indicating that they are not essential during primary tumor formation at either site. SK-N-SH cells (with diploid N-myc) express beta 1, alpha 2, and alpha 3 subunits of expected sizes (with alpha 2 uncleaved at 145 kDa) but do not express alpha 1, alpha 4, alpha 5, alpha V, or beta 3. This expression pattern was conserved in all first-round subcutaneous and adrenal tumor cell populations, as well as in second-round subcutaneous tumors derived from a first-round subcutaneous tumor (no tumors expressed beta 3). One significant difference was noted between subcutaneous and adrenal tumor populations: all first- and second-round subcutaneous tumors expressed high levels of alpha V subunit, while adrenal tumors did not express any alpha V. This result suggests some essential function for alpha V beta 1 during subcutaneous primary tumor formation. Integrin patterns were also evaluated by fluorescence-activated cell sorting. SK-N-SH and its derivative tumors expressed heterogeneous amounts of beta 1 and alpha 2 at the cell surface, while only subcutaneous tumor cells expressed alpha V. Parental SK-N-SH cells contained two subpopulations, half of which expresses alpha 3, while the other half does not; all subcutaneous tumor cells retained this two-subpopulation pattern, indicating that primary tumor formation does not lead to clonal dominance of alpha 3(-) or alpha 3(+) cell types in larger primary tumors. While these results suggest a correlation between N-myc amplification and down-regulation of integrin expression in neuroblastoma, they demonstrate conservation of integrin expression during two rounds of primary tumor formation at ectopic or orthotopic sites in a mouse model system, induction and/or selection for alpha V beta 1 expression at the subcutaneous site, and clonal heterogeneity in alpha 3 beta 1 expression throughout primary tumor development. (C) 1994 Academic Press, Inc.