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一种表达Erb B家族受体和白细胞介素-6的新型人乳腺癌细胞系KPL-4的分离与鉴定。

Isolation and characterization of a new human breast cancer cell line, KPL-4, expressing the Erb B family receptors and interleukin-6.

作者信息

Kurebayashi J, Otsuki T, Tang C K, Kurosumi M, Yamamoto S, Tanaka K, Mochizuki M, Nakamura H, Sonoo H

机构信息

Department of Breast and Thyroid Surgery, Kawasaki Medical School, Kurashiki, Okayama, Japan.

出版信息

Br J Cancer. 1999 Feb;79(5-6):707-17. doi: 10.1038/sj.bjc.6690114.

Abstract

A new human breast cancer cell line, KPL-4, was recently isolated from the malignant pleural effusion of a breast cancer patient with an inflammatory skin metastasis. This cell line can be cultured under serum-free conditions and is tumorigenic in female athymic nude mice. Flow cytometric analysis revealed the expression of Erb B-1, -2 and -3. Dot blot hybridization showed a 15-fold amplification of the erb B-2. Reverse transcription-polymerase chain reaction analysis showed a detectable level of mRNA expression of all the Erb B family receptors. In addition, all the receptors were autophosphorylated under a serum-supplemented condition. Unexpectedly, transplanted KPL-4 tumours induced cachexia of recipient mice. A high concentration of interleukin-6 (IL-6) was detected in both the culture medium and the serum of mice. The weight of tumours significantly correlated with the serum IL-6 level. The antiproliferative effect of a humanized anti-Erb B-2 monoclonal antibody, rhuMAbHER2, was investigated. This antibody significantly inhibited the growth of KPL-4 cells in vitro but modestly in vivo. Loss of mouse body weight was partly reversed by rhuMAbHER2. These findings suggest that KPL-4 cells may be useful in the development of new strategies against breast cancer overexpressing the Erb B family receptors and against IL-6-induced cachexia.

摘要

一种新的人乳腺癌细胞系KPL-4,最近从一名患有炎性皮肤转移的乳腺癌患者的恶性胸腔积液中分离出来。该细胞系可在无血清条件下培养,并且在雌性无胸腺裸鼠中具有致瘤性。流式细胞术分析显示Erb B-1、-2和-3的表达。斑点印迹杂交显示erb B-2有15倍的扩增。逆转录-聚合酶链反应分析显示所有Erb B家族受体的mRNA表达水平均可检测到。此外,在补充血清的条件下,所有受体均发生自身磷酸化。出乎意料的是,移植的KPL-4肿瘤诱导受体小鼠出现恶病质。在小鼠的培养基和血清中均检测到高浓度的白细胞介素-6(IL-6)。肿瘤重量与血清IL-6水平显著相关。研究了人源化抗Erb B-2单克隆抗体rhuMAbHER2的抗增殖作用。该抗体在体外显著抑制KPL-4细胞的生长,但在体内作用较弱。rhuMAbHER2部分逆转了小鼠体重的减轻。这些发现表明,KPL-4细胞可能有助于开发针对过表达Erb B家族受体的乳腺癌以及针对IL-6诱导的恶病质的新策略。

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