Vitamin D compounds reduce mammosphere formation and decrease expression of putative stem cell markers in breast cancer.
Vitamin D compounds reduce mammosphere formation and decrease expression of putative stem cell markers in breast cancer.
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DOI：
10.1016/j.jsbmb.2014.10.016
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发表时间：
2015-04
影响因子：
4.1
通讯作者：
Suh, Nanjoo
中科院分区：
文献类型：
--
作者：
Wahler, Joseph;So, Jae Young;Cheng, Larry C.;Maehr, Hubert;Uskokovic, Milan;Suh, Nanjoo
乳腺癌干细胞（BCSC）是肿瘤细胞的一个亚群，被认为是负责肿瘤建立和维持的细胞。此外，BCSC被认为是癌症进展到转移和复发的主要原因，因为它们的肿瘤引发能力和对常规治疗的抗性。乳腺导管原位癌（DCIS）是乳腺癌发生的早期先兆，可发展为浸润性导管癌（IDC）。我们以前曾报道，维生素D化合物BXL 0124可抑制DCIS向IDC的进展。在本研究中，我们试图确定这种效应是否是通过对BCSC的影响介导的。在用维生素D化合物（1α25（OH）2D 3或BXL 0124）处理的MCF 10 DCIS细胞中，通过CD 44 +/CD 24-/低和CD 49 f +/CD 24-/低亚群识别的乳腺癌干细胞样群体减少。为了确定维生素D化合物对癌症干细胞活性的影响，利用了富集乳腺祖细胞和推定的BCSC的MCF 10 DCIS乳腺球细胞培养系统。未经处理的MCF 10 DCIS乳腺球显示出无序和不规则的形状。当用1α25（OH）2D 3或BXL 0124处理MCF 10 DCIS细胞时，形成的乳腺球表现出更有组织、对称和圆形的形状，类似于由非恶性、正常乳腺上皮细胞系MCF 10A形成的球的外观。经1α25（OH）2D 3或BXL 0124处理后，乳腺球形成效率（MFE）显著降低，表明这些化合物对乳腺球发育具有抑制作用。用1α25（OH）2D 3或BXL 0124处理抑制了与干细胞样表型相关的标志物，如CD 44、CD 49 f、c-Notch 1和pNFκB。此外，1α25（OH）2D 3和BXL 0124降低了乳腺球中多能性标志物OCT 4和KLF-4的表达。这项研究表明，维生素D化合物抑制乳腺癌干细胞样群体，可能有助于抑制乳腺癌。
Breast cancer stem cells (BCSCs) are a subset of tumor cells that are believed to be the cells responsible for the establishment and maintenance of tumors. Moreover, BCSCs are suggested to be the main cause of progression to metastasis and recurrence of cancer because of their tumor-initiating abilities and resistance to conventional therapies. Ductal carcinoma in situ (DCIS) is an early precursor in breast carcinogenesis which progresses to invasive ductal carcinoma (IDC). We have previously reported that a vitamin D compound, BXL0124, inhibits the progression of DCIS to IDC. In the present study we sought to determine whether this effect was mediated through an influence on BCSCs. In MCF10DCIS cells treated with vitamin D compounds (1α25(OH)2D3 or BXL0124), the breast cancer stem cell-like population, identified by the CD44+/CD24−/low and CD49f+/CD24−/low subpopulations, was reduced. To determine the effects of vitamin D compounds on cancer stem cell activity, the MCF10DCIS mammosphere cell culture system, which enriches for mammary progenitor cells and putative BCSCs, was utilized. Untreated MCF10DCIS mammospheres showed a disorganized and irregular shape. When MCF10DCIS cells were treated with 1α25(OH)2D3 or BXL0124, the mammospheres that formed exhibited a more organized, symmetrical and circular shape, similar to the appearance of spheres formed by the non-malignant, normal mammary epithelial cell line, MCF10A. The mammosphere forming efficiency (MFE) was significantly decreased upon treatment with 1α25(OH)2D3 or BXL0124, indicating that these compounds have an inhibitory effect on mammosphere development. Treatment with 1α25(OH)2D3 or BXL0124 repressed markers associated with the stem cell-like phenotype, such as CD44, CD49f, c-Notch1, and pNFκB. Furthermore, 1α25(OH)2D3 and BXL0124 reduced the expression of pluripotency markers, OCT4 and KLF-4 in mammospheres. This study suggests that vitamin D compounds repress the breast cancer stem cell-like population, potentially contributing to their inhibition of breast cancer.
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影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
影响因子：
7.4
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Purushotham, Anand D.
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影响因子：
21.3
作者：
Asselin-Labat, Marie-Liesse;Sutherland, Kate D.;Visvader, Jane E.
通讯作者：
Visvader, Jane E.