Cancer stem cells and early stage basal-like breast cancer.
Cancer stem cells and early stage basal-like breast cancer.
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DOI：
10.5317/wjog.v5.i2.150
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发表时间：
2016-05-10
期刊：
影响因子：
--
通讯作者：
Zhou Q
中科院分区：
文献类型：
--
作者：
Lo PK;Wolfson B;Zhou Q
乳腺导管原位癌(DCIS)是一种早期的非侵袭性乳腺肿瘤，定义为乳腺恶性上皮细胞在导管内的增殖。DCIS是一种由多种分子亚型组成的异质性疾病，包括Lumina、HER2和基底样型，其特征是免疫组织化学分析和基因表达谱。在手术和放射治疗之后，管腔型、雌激素受体阳性的DCIS乳腺肿瘤患者可以从基于内分泌的辅助治疗中受益。然而，由于缺乏内分泌受体和HER2扩增，目前还没有针对基底样直肠癌(BLDCIS)患者的靶向治疗，这使得他们容易复发。此外，多条证据表明，DCIS是浸润性乳腺癌的非专性先兆。这增加了靶向前体BLDCIS是预防BLDCIS患者发展为浸润性基底细胞样乳腺癌的一种有前景的策略的可能性。越来越多的证据表明，在BL-DCIS中存在癌症干细胞(CSCs)，这可能决定了BL-DCIS的特征及其发展为侵袭性癌症的能力。本文就BLDCIS的特点、神经干细胞的鉴定及其生物学特性等方面的研究进展作一综述。我们综述了最近发现的促进BLDCIS中CSCs产生和BLDCIS向浸润性乳腺癌发展的相关分子信号变化，以及组织微环境对CSCs和侵袭性转变的影响。最后，我们讨论了这些发现对预测和预防BLDCIS复发和进展的翻译意义。
Ductal carcinoma in situ (DCIS) is a category of early stage, non-invasive breast tumor defined by the intraductal proliferation of malignant breast epithelial cells. DCIS is a heterogeneous disease composed of multiple molecular subtypes including luminal, HER2 and basal-like types, which are characterized by immunohistochemical analyses and gene expression profiling. Following surgical and radiation therapies, patients with luminal-type, estrogen receptor-positive DCIS breast tumors can benefit from adjuvant endocrine-based treatment. However, there are no available targeted therapies for patients with basal-like DCIS (BL-DCIS) tumors due to their frequent lack of endocrine receptors and HER2 amplification, rendering them potentially susceptible to recurrence. Moreover, multiple lines of evidence suggest that DCIS is a non-obligate precursor of invasive breast carcinoma. This raises the possibility that targeting precursor BL-DCIS is a promising strategy to prevent BL-DCIS patients from the development of invasive basal-like breast cancer. An accumulating body of evidence demonstrates the existence of cancer stem-like cells (CSCs) in BL-DCIS, which potentially determine the features of BL-DCIS and their ability to progress into invasive cancer. This review encompasses the current knowledge in regard to the characteristics of BL-DCIS, identification of CSCs, and their biological properties in BL-DCIS. We summarize recently discovered relevant molecular signaling alterations that promote the generation of CSCs in BL-DCIS and the progression of BL-DCIS to invasive breast cancer, as well as the influence of the tissue microenvironment on CSCs and the invasive transition. Finally, we discuss the translational implications of these findings for the prognosis and prevention of BL-DCIS relapse and progression.