Researchers have made significant strides in the field of breast cancer treatment by successfully establishing methodologies for the selective culture of breast cancer stem cells (BCSCs). A recent study published on March 10, 2025, explores the inherent diversity of these stem cells, focusing on surgical samples from treatment-naïve patients diagnosed with estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This effort highlights the potential for innovative therapeutic strategies targeting the challenging population of breast cancer stem cells.
Breast cancer stem cells are notorious for their capacity for self-renewal and their contribution to the development of metastatic lesions. They also exhibit resistance to conventional anticancer therapies, thereby amplifying the risks of recurrence and metastasis. Given these obstacles, they emerge as key targets for effective cancer treatment. The researchers sought to selectively culture these cells from breast cancer tissues, shedding light on their unique properties and variations.
This comprehensive study, led by Sueoka et al., successfully cultured breast cancer stem cells from 48 out of 57 patient cases (an impressive success rate of 84.2%). Utilizing spheroid culture techniques on non-adhesive plates at low cell densities, the researchers achieved selective growth of BCSCs, highlighting their potential biological characteristics.
Significant findings from the study include the observation of increased ratios of CD44+/CD24− cells, which are indicative of breast cancer stem cells. This ratio rose dramatically from 13.8% within primary tumor samples to 61.6% after spheroid culture. Such transformations signify not only the successful isolation of stem-like cells but also their enhanced stemness—a condition corroborated by subsequent analysis.
Among the most notable changes, the study revealed alterations to hormone receptor statuses. Specifically, 52.1% of the cases experienced negative conversion of ER expression. Among other markers, the proportion of Twist+, Snail+, and Vimentin+ cells also increased significantly, reflecting the epithelial-mesenchymal transition (EMT)—a transformative process where cancer cells gain mobility, contributing to invasiveness.
"We successfully established a method to selectively culture breast cancer stem cells from patient-derived breast cancer tissues, achieving a markedly high success rate (84.2%; 48/57 cases)," remarked the authors of the article. This assertion emphasizes the study's validity and reproducibility across multiple surgical specimens.
The research categorized ER-positive, HER2-negative breast cancer stem cells using DNA microarray analysis, resulting in the identification of two distinct groups. One such group exhibited heightened expression of immune response-related genes, which offers exciting pathways for developing targeted immunotherapies.
The methodology showcased significant advancements as well. Thin tumor sections were procured and treated with enzymatic solutions, followed by culturing under specific temperature and carbon dioxide conditions. This level of intricacy allowed for the optimal reproduction of cellular dynamics reflective of the tumor microenvironment.
Following the establishment of these patient-derived stem cell xenografts (PDSXs), which occurred successfully for 5 out of the 11 samples transplanted, the study demonstrated the proliferative nature of these spheroid-cultured cells. Tumor formation was achieved when transplanted, paving the way for potential therapeutic evaluations.
Detailed comparisons of changes between primary tumors, spheroids, and xenografts revealed noteworthy patterns. The study established tolerances for cell transplantation without compromising the translational viability of endotherapy options. Through these assessments, the researchers aim to contribute to personalized breast cancer pharmacotherapy approaches.
The insights garnered from this study are poised to not only refine our comprehension of BCSCs but also facilitate advancements toward curative treatments for breast cancer. By tailoring therapeutic solutions based on the unique genetic and phenotypic features of breast cancer stem cells, there may be significant improvements to patient outcomes, particularly for individuals with advanced or recurrent disease.
Although the research is commendable, researchers acknowledge certain limitations. The focus remains solely on ER-positive and HER2-negative cases, potentially restricting the applicability of findings across all breast cancer subtypes. Continual exploration of spheroid culture methods may yield comprehensive frameworks for evaluating varying breast cancer types.
By validating methodologies for selectively isolATING breast cancer stem cells and outlining their extensive biological diversity, this study lays the groundwork for future investigations aimed at integrating stem cell-targeted therapies. Enhancing the effectiveness of current treatments by manipulating differentiation pathways stands as the ultimate goal in combating the challenges posed by metastatic breast cancer.