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Breast Cancer Res:乳腺癌新型生物标志物及治疗靶点

  1. IL13RA2
  2. 三阴性乳腺癌
  3. 生物标志物
  4. 靶点

来源:生物谷 2015-08-04 18:47

一篇发表于国际杂志Breast Cancer Research上的研究报告中,来自波士顿大学医学院的研究者开发出了一种新型方法,其或许可以帮助检测/治疗恶性乳腺癌。

2015年8月3日 讯 /生物谷BIOON/ --一篇发表于国际杂志Breast Cancer Research上的研究报告中,来自波士顿大学医学院的研究者开发出了一种新型方法,其或许可以帮助检测/治疗恶性乳腺癌。

基底细胞样型乳腺癌 (Basal-like breast cancer,BLBC)是一种恶性乳腺癌,其通常被成为三阴性乳腺癌,这就意味着这种恶性乳腺癌对于常见的医疗手段并没有任何反应;基底细胞样型乳腺癌更容易发生转移,快速且容易扩散到机体其它部位,而且疾病预后往往较差。40岁以下女性及非洲裔美国女性更容易患这种类型的乳腺癌,但截至目前为止研究者并没有有效的疗法来治疗该类乳腺癌。

其中一项巨大挑战就是鉴别转移性BLBC的特殊标志物,这可以帮助开发新型治疗性药物及预测患者的治疗情况;文章中研究者通过利用公共数据库的信息,对比了癌细胞表面的标志物及肿瘤细胞的基因表达特性,结果发现了一种名为IL13RA2的分子在转移性的BLBC或晚期的BLBC患者机体中含量丰富;当对患者的公共可用数据进行分析后,研究者就可以基于癌细胞中是否含有高水平的IL13RA2分子来预测出患者疾病的无恶化生存率,同时研究小组还发现可以快速扩散到肺部的BLBC亚型肿瘤细胞中也含有较高水平的IL13RA2分子。

当研究者减少癌细胞中IL13RA2分子的表达时,他们发现模型中肿瘤的生长明显减缓了,而接受修饰后的癌细胞的模型就表现出了癌症很少或基本不会转移到肺部组织,这就表明IL13RA2分子参与了癌症的生长和扩散。Sam Thiagalingam博士说道,本文研究为开发BLBC患者的新型疗法提供了新的思路,而通过靶向作用表达高水平IL13RA2分子的乳腺癌细胞,研究者或可开发出新型的个体化癌症疗法。

当然本文研究并不会止于研究乳腺癌,其它致死性癌症,比如脑癌、胰腺癌等癌症中癌细胞也会表达出高水平的IL13RA2分子,这就揭示了该分子作为标志物的重要性;进行IL13RA2分子检测的研究或可帮助改善多种致死性癌症的诊断,后期研究者还需要进行更多的研究不仅来理解IL13RA2分子,还将理解其它多种分子在乳腺癌发展中的角色,为后期开发指导、诊断及治疗乳腺癌的新策略或将带来巨大的帮助。(生物谷Bioon.com)

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Targeting IL13Ralpha2 activates STAT6-TP63 pathway to suppress breast cancer lung metastasis n

Panagiotis Papageorgis1, 2, 3 , Sait Ozturk2 , Arthur W. Lambert2 , Christiana M. Neophytou1 , Alexandros Tzatsos4 , Chen K. Wong2 , Sam Thiagalingam2 and Andreas I. Constantinou1

Introduction Basal-like breast cancer (BLBC) is an aggressive subtype often characterized by distant metastasis, poor patient prognosis, and limited treatment options. Therefore, the discovery of alternative targets to restrain its metastatic potential is urgently needed. In this study, we aimed to identify novel genes that drive metastasis of BLBC and to elucidate the underlying mechanisms of action. Methods An unbiased approach using gene expression profiling of a BLBC progression model and in silico leveraging of pre-existing tumor transcriptomes were used to uncover metastasis-promoting genes. Lentiviral-mediated knockdown of interleukin-13 receptor alpha 2 (IL13Ralpha2) coupled with whole-body in vivo bioluminescence imaging was performed to assess its role in regulating breast cancer tumor growth and lung metastasis. Gene expression microarray analysis was followed by in vitro validation and cell migration assays to elucidate the downstream molecular pathways involved in this process. Results We found that overexpression of the decoy receptor IL13Ralpha2 is significantly enriched in basal compared with luminal primary breast tumors as well as in a subset of metastatic basal-B breast cancer cells. Importantly, breast cancer patients with high-grade tumors and increased IL13Ralpha2 levels had significantly worse prognosis for metastasis-free survival compared with patients with low expression. Depletion of IL13Ralpha2 in metastatic breast cancer cells modestly delayed primary tumor growth but dramatically suppressed lung metastasis in vivo. Furthermore, IL13Ralpha2 silencing was associated with enhanced IL-13-mediated phosphorylation of signal transducer and activator of transcription 6 (STAT6) and impaired migratory ability of metastatic breast cancer cells. Interestingly, genome-wide transcriptional analysis revealed that IL13Ralpha2 knockdown and IL-13 treatment cooperatively upregulated the metastasis suppressor tumor protein 63 (TP63) in a STAT6-dependent manner. These observations are consistent with increased metastasis-free survival of breast cancer patients with high levels of TP63 and STAT6 expression and suggest that the STAT6-TP63 pathway could be involved in impairing metastatic dissemination of breast cancer cells to the lungs. Conclusion Our findings indicate that IL13Ralpha2 could be used as a promising biomarker to predict patient outcome and provide a rationale for assessing the efficacy of anti-IL13Ralpha2 therapies in a subset of highly aggressive basal-like breast tumors as a strategy to prevent metastatic disease.

相关会议:2015生物标志物研讨会

http://www.bioon.com/z/2015biomarker/

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