Grossman Deborah A, Hiti Alan L, McNiel Elizabeth A, Ye Yin, Alpaugh Mary L, Barsky Sanford H
Department of Pathology, University of California-Los Angeles School of Medicine, Los Angeles, California 90024, USA.
Cancer Res. 2002 Jul 1;62(13):3826-33.
Although certain neoplasms are unique to man, others occur across species. One such neoplasm is bronchioloalveolar lung carcinoma (BAC), a neoplasm of the Type II pneumocyte that affects humans, sheep, and small animals (dogs and cats). Human BAC occurs largely in nonsmokers. Sheep BAC is caused by the jaagsiekte retrovirus and is endemic and contagious. Feline BAC is neither endemic nor contagious and occurs sporadically and spontaneously in older purebred cats. In these respects, feline BAC is more closely similar to human BAC than sheep BAC (jaagsiekte) is. To study feline BAC further, we established the first immortal cell line (SPARKY) and transplantable scid mouse xenograft (Sparky-X) from a malignant pleural effusion of a 12-year-old Persian male with autopsy-confirmed BAC. SPARKY exhibited a Type II pneumocyte phenotype characterized by surfactant and thyroid-transcription factor-1 immunoreactivities and lamellar bodies. SPARKY's karyotype was aneuploid (66 chromosomes: 38, normal cat) and showed evidence of genomic instability analogous to human lung cancers. p53 showed a homozygous G to T transversion at codon 167, the feline equivalent of human codon 175, one of the many hot spots mutated in the lung cancers of smokers. H-ras and K-ras were not altered. By reverse transcription-PCR, SPARKY lacked expression of retroviral JSRVgag transcripts that were present in the lungs of sheep BAC (jaagsiekte). Unlike human BAC xenografts, SPARKY-X retained its unique lepidic BAC growth pattern even though it was grown in murine s.c. tissues. This property may be related to the ability of SPARKY-X to up-regulate its surfactant genes (SP-A, SP-B, and SP-D). These studies of feline BAC may allow insights into the human disease that are not possible by studying human BAC directly.
尽管某些肿瘤是人类特有的，但其他肿瘤则跨物种发生。其中一种肿瘤是细支气管肺泡肺癌（BAC），它是一种影响人类、绵羊和小型动物（狗和猫）的II型肺细胞肿瘤。人类BAC主要发生在不吸烟者中。绵羊BAC由绵羊肺腺瘤逆转录病毒引起，具有地方性和传染性。猫BAC既无地方性也无传染性，在老年纯种猫中偶尔自发发生。在这些方面，猫BAC比绵羊BAC（绵羊肺腺瘤病）更类似于人类BAC。为了进一步研究猫BAC，我们从一只经尸检确诊为BAC的12岁波斯雄性猫的恶性胸腔积液中建立了首个永生细胞系（SPARKY）和可移植的严重联合免疫缺陷小鼠异种移植瘤（Sparky-X）。SPARKY表现出II型肺细胞表型，其特征为表面活性物质和甲状腺转录因子-1免疫反应性以及板层小体。SPARKY的核型为非整倍体（66条染色体：正常猫为38条），并显示出与人类肺癌类似的基因组不稳定性证据。p53在第167密码子处显示纯合的G到T颠换，相当于人类第175密码子，这是吸烟者肺癌中许多发生突变的热点之一。H-ras和K-ras未发生改变。通过逆转录聚合酶链反应，SPARKY缺乏绵羊BAC（绵羊肺腺瘤病）肺中存在的逆转录病毒JSRVgag转录本的表达。与人类BAC异种移植瘤不同，即使在小鼠皮下组织中生长，Sparky-X仍保留其独特的鳞屑状BAC生长模式。这一特性可能与Sparky-X上调其表面活性物质基因（SP-A、SP-B和SP-D）的能力有关。这些对猫BAC的研究可能使我们深入了解人类疾病，而直接研究人类BAC则无法做到这一点。
