4种新的人胰腺癌细胞系的建立与鉴定：不同肿瘤表型的证据

Establishment and characterization of 4 new human pancreatic cancer cell lines: evidences of different tumor phenotypes.

作者信息

Chifenti Barbara, Morelli Mariangela, Zavaglia Michele, Coviello Domenico A, Guerneri Silvana, Santucci Annalisa, Paffetti Alessandro, Masetti Massimo, Locci Maria Teresa, Bertacca Gloria, Capodanno Alessandra, Collecchi Paola, Campani Daniela, Mosca Franco, Bevilacqua Generoso, Cavazzana Andrea O

机构信息

Division of Surgical, Regional Referral Center for Pancreatic Diseases Treatment, Azienda Ospedaliera Universitaria Pisana, University of Pisa, Pisa, Italy.

出版信息

Pancreas. 2009 Mar;38(2):184-96. doi: 10.1097/MPA.0b013e31818c746a.

DOI:10.1097/MPA.0b013e31818c746a

PMID:19002021

Abstract

OBJECTIVES

Pancreatic cancer still remains a challenge for its biological complexity and lack of effective therapeutic strategies. Establishing new pancreatic cancer cell lines is therefore of paramount importance to clarify its biology.

METHODS

We established and characterized 4 new pancreatic cancer cell lines (PP78, PP109, PP117, and PP161) according to their genetic (K-Ras, TP53, CDKN2A, and MADH4; DNA fingerprinting; karyotype), cytostructural (cytokeratins 7, 8, 18, and 19 vimentin, and ezrin), and functional profiles (doubling time; migration assay).

RESULTS

K-Ras, TP53, and CDKN2A gene alterations were detected in all 4 of them. Each cell line had a unique DNA profile revealed by DNA fingerprinting. A complex karyotype with numerous structural and numeric chromosomal abnormalities was present in each cell line. All 4 cell lines showed positivity for cytokeratins 7, 8, and 18. All but PP78 expressed cytokeratin 19, whereas vimentin was expressed only in PP117 and PP78 cells. A different ezrin cellular distribution was noticed in PP78 and PP117, being mostly located at membrane ruffles. This peculiar distribution was associated with the strongest migratory capability.

CONCLUSIONS

Our results seem to confirm the pancreatic ductal adenocarcinoma heterogeneity; in fact, the same genetic abnormalities (K-Ras, TP53, and CDKN2A) may have different effects on tumor biology depending on cellular differentiation.

摘要

目的

胰腺癌因其生物学复杂性和缺乏有效的治疗策略，仍然是一个挑战。因此，建立新的胰腺癌细胞系对于阐明其生物学特性至关重要。

方法

我们根据4种胰腺癌细胞系（PP78、PP109、PP117和PP161）的遗传学特征（K-Ras、TP53、CDKN2A和MADH4；DNA指纹图谱；核型）、细胞结构特征（细胞角蛋白7、8、18和19、波形蛋白和埃兹蛋白）和功能特征（倍增时间；迁移试验）对其进行了建立和表征。

结果

在所有4种细胞系中均检测到K-Ras、TP53和CDKN2A基因改变。通过DNA指纹图谱揭示，每个细胞系都有独特的DNA谱型。每个细胞系都存在具有众多结构和数量染色体异常的复杂核型。所有4种细胞系对细胞角蛋白7、8和18均呈阳性。除PP78外，所有细胞系均表达细胞角蛋白19，而波形蛋白仅在PP117和PP78细胞中表达。在PP78和PP117中观察到埃兹蛋白的细胞分布不同，主要位于膜皱褶处。这种特殊分布与最强的迁移能力相关。