Dr. Weeks’ Comment: Light and Vitamin D3 block the lethal work of the breast cancer STEM cell. “Free the ladies” this summer (or just take supplemental vitamin D3 until your levels are optimal – make certain to have your vitamin D3 level taken – the blood test is 25-OH D3).
Vitamin D compounds reduce mammosphere formation and decrease expression of putative stem cell markers in breast cancer
The Journal of Steroid Biochemistry and Molecular Biology Volume 148, April 2015, Pages 148-155 17th Vitamin D Workshop
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 (1Î±25(OH)2D3 or BXL0124), the breast cancer stem cell-like population, identified by the CD44+/CD24âˆ’/lowand CD49f+/CD24âˆ’/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 1Î±25(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 1Î±25(OH)2D3 or BXL0124, indicating that these compounds have an inhibitory effect on mammosphere development. Treatment with 1Î±25(OH)2D3 or BXL0124 repressed markers associated with the stem cell-like phenotype, such as CD44, CD49f, c-Notch1, and pNFÎºB. Furthermore, 1Î±25(OH)2D3and 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.