細(xì)胞的培養(yǎng)是均一的,，然而人類的腫瘤卻不是這樣。近日來自美國科羅拉多大學(xué)癌癥中心的研究者報(bào)道了,，人體雌激素陽性（ER+）乳腺癌模型可以保留其異質(zhì)性,，允許科學(xué)家更精確地運(yùn)用測試藥物來檢測疾病。相關(guān)研究成果刊登在了近日的國際雜志Breast Cancer Research and Treatment上,。
“乳腺癌從來沒有黑白之分，這些模型允許我們將其中的灰色部分挑選出來”,，研究者Peter這樣說,，他的意思是并不是所有的人體雌激素陽性乳腺癌細(xì)胞都是雌激素陽性的。相反在人類腫瘤細(xì)胞中,，它們或許是依賴雌激素生存的細(xì)胞,，而且對(duì)于抗雌激素療法比較敏感。在同質(zhì)ER+細(xì)胞培養(yǎng)液中檢測測試藥物或許幾乎不能預(yù)測藥物是如何對(duì)異質(zhì)腫瘤細(xì)胞進(jìn)行作用的,。
這種異質(zhì)性所引發(fā)的乳腺癌大部分具有致命性的特征-有抗雌激素藥物的能力,。理論上來說，醫(yī)生可以用抗雌激素藥物來殺滅ER+細(xì)胞,，但是這并不能減緩其他類型乳腺癌細(xì)胞的生長,，這些乳腺癌細(xì)胞或許將來會(huì)變成主要的癌癥細(xì)胞類型，這些ER-細(xì)胞更趨向于很難殺滅,。
這種新型的異質(zhì)乳腺癌細(xì)胞模型為研究者們帶來了兩件事情,，第一，研究者可以更精確地檢測藥物的有效性,；第二,，相比尋找常見乳腺癌的特征，維持這些腫瘤的異質(zhì)性使得研究者研究什么對(duì)于腫瘤是唯一的,。
近日的研究中,，經(jīng)過外科手術(shù)所得到的人類乳腺腫瘤樣品被移植進(jìn)入動(dòng)物模型中，腫瘤同樣可以維持其異質(zhì)性,。研究者Kabos表示,，下一步的治療方法將幫助我們理解在腫瘤中ER+和ER-的比例,，并且?guī)椭覀兘饷芷湔{(diào)節(jié)機(jī)制。（生物谷Bioon.com）
編譯自：Heterogeneous ER breast cancer models allow more accurate drug testing
doi:10.1007/s10549-012-2164-8
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PMID:
Patient-derived luminal breast cancer xenografts retain hormone receptor heterogeneity and help define unique estrogen-dependent gene signatures
Peter Kabos, Jessica Finlay-Schultz, Chunling Li, Enos Kline, Christina Finlayson, Joshua Wisell, Christopher A. Manuel, Susan M. Edgerton, J. Chuck Harrell and Anthony Elias, et al.
Bypassing estrogen receptor (ER) signaling during development of endocrine resistance remains the most common cause of disease progression and mortality in breast cancer patients. To date, the majority of molecular research on ER action in breast cancer has occurred in cell line models derived from late stage disease. Here we describe patient-derived ER+ luminal breast tumor models for the study of intratumoral hormone and receptor action. Human breast tumor samples obtained from patients post surgery were immediately transplanted into NOD/SCID or NOD/SCID/ILIIrg−/− mice under estrogen supplementation. Five transplantable patient-derived ER+ breast cancer xenografts were established, derived from both primary and metastatic cases. These were assessed for estrogen dependency, steroid receptor expression, cancer stem cell content, and endocrine therapy response. Gene expression patterns were determined in select tumors ±estrogen and ±endocrine therapy. Xenografts morphologically resembled the patient tumors of origin, and expressed similar levels of ER (5–99 %), and progesterone and androgen receptors, over multiple passages. Four of the tumor xenografts were estrogen dependent, and tamoxifen or estrogen withdrawal (EWD) treatment abrogated estrogen-dependent growth and/or tumor morphology. Analysis of the ER transcriptome in select tumors revealed notable differences in ER mechanism of action, and downstream activated signaling networks, in addition to identifying a small set of common estrogen-regulated genes. Treatment of a naïve tumor with tamoxifen or EWD showed similar phenotypic responses, but relatively few similarities in estrogen-dependent transcription, and affected signaling pathways. Several core estrogen centric genes were shared with traditional cell line models. However, novel tumor-specific estrogen-regulated potential target genes, such as cancer/testis antigen 45, were uncovered. These results evoke the importance of mapping both conserved and tumor-unique ER programs in breast cancers. Furthermore, they underscore the importance of primary xenografts for improved understanding of ER+ breast cancer heterogeneity and development of personalized therapies.
