In vivo overexpression of IL-13 receptor alpha2 chain inhibits tumorigenicity of human breast and pancreatic tumors in immunodeficient mice.
In vivo overexpression of IL-13 receptor alpha2 chain inhibits tumorigenicity of human breast and pancreatic tumors in immunodeficient mice.
复制标题
DOI：
10.1084/jem.194.12.1743
复制
发表时间：
2001-12-17
期刊：
影响因子：
--
通讯作者：
Puri RK
中科院分区：
文献类型：
--
作者：
Kawakami K;Kawakami M;Snoy PJ;Husain SR;Puri RK
白细胞介素13受体α2（IL-13 R α2）链在一些肿瘤细胞系和原代细胞培养物中高度表达。该受体链在配体结合和内化中起重要作用。为了确定该链过表达的功能意义，我们将IL-13 R α2链稳定转染到天然不表达该链的人乳腺癌（MDA-MB-231）和胰腺癌（PANC-1）细胞系中。转染IL-13 R α2链的细胞与单纯转染IL-13 R α2链的细胞在体外生长无明显差异。然而，令人惊讶的是，在免疫缺陷小鼠中，致瘤性在IL-13 R α2链过表达肿瘤中被显著抑制。由于生长较晚的乳腺肿瘤显示IL-13 R α2基因表达缺失，致瘤性缺失与IL-13 R α2链表达呈正相关。在IL-13 R α2过表达的消退肿瘤中鉴别出包括中性粒细胞和巨噬细胞在内的炎性细胞，发现中性粒细胞产生IL-13。IL-13对IL-13 R α2链过表达的肿瘤在体内外均表现出一定的抗肿瘤活性。此外，IL-13 R α2链过表达肿瘤组成性产生IL-8，已显示具有抗肿瘤作用。这些结果建立了一个新的功能的细胞因子受体链，并进一步表明，这种链的存在下，肿瘤细胞本身可能在致瘤性中发挥关键作用。
Interleukin 13 receptor α2 (IL-13Rα2) chain is highly expressed on some tumor cell lines and primary cell cultures. This receptor chain plays an important role in ligand binding and internalization. To determine the functional significance of overexpression of this chain, we stably transfected IL-13Rα2 chain in human breast (MDA-MB-231) and pancreatic (PANC-1) cancer cell lines that naturally do not express this chain. There was no difference in growth between vector only transfected and IL-13Rα2 chain transfected cells in vitro. However, surprisingly, in immunodeficient mice, tumorigenicity was profoundly inhibited in IL-13Rα2 chain overexpressing tumors. Because breast tumors that grew later showed loss of IL-13Rα2 gene expression, lack of tumorigenicity correlated positively with IL-13Rα2 chain expression. Inflammatory cells including neutrophils and macrophages were identified in IL-13Rα2 overexpressing regressing tumors and neutrophils were found to produce IL-13. IL-13 showed a modest antitumor activity to IL-13Rα2 chain overexpressing tumors in vitro and in vivo. Furthermore, IL-13Rα2 chain overexpressing tumors constitutively produced IL-8 that has been shown to have antitumor effect. These results establish a novel function of a cytokine receptor chain and further suggest that the presence of this chain on tumor cells by itself may play a key role in tumorigenicity.
登录
查看更多内容
DOI：
10.1084/jem.184.2.569
发表时间：
1996-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Loetscher P;Seitz M;Baggiolini M;Moser B
通讯作者：
Moser B
影响因子：
3.2
作者：
Murad, AM;deAndrade, CA;Sinha, N
通讯作者：
Sinha, N
影响因子：
4.8
作者：
Caput, D;Laurent, P;Ferrara, P
通讯作者：
Ferrara, P
影响因子：
4.8
作者：
DEBINSKI, W;OBIRI, NI;PURI, RK
通讯作者：
PURI, RK
影响因子：
4.8
作者：
Kawakami, K;Takeshita, F;Puri, RK
通讯作者：
Puri, RK