In the latest issue of the Journal of Histotechnology, Mohamed M. Haq, Curtis Benson, Meik Kunz, and Elim Y.L. Cheung explore how myoepithelial cells (MECs), long recognized as protective cells within the breast, may undergo significant molecular changes during invasive breast cancer progression. In the article," Unraveling myoepithelial cell plasticity in breast cancer: a transcriptomic approach," the authors use advanced spatial transcriptomic technology, and provide new evidence that these cells may shift from a tumor-suppressive role to one that potentially supports tumor growth and invasion.
Understanding the Role of Myoepithelial Cells
Myoepithelial cells form a specialized layer surrounding breast ducts and lobules. In healthy breast tissue, they provide structural support, maintain tissue organization, contribute to basement membrane integrity, and help suppress tumor development through the secretion of protective proteins and signaling molecules.
Previous studies have demonstrated that MECs become functionally altered in ductal carcinoma in situ (DCIS), but little was known about their behavior in invasive breast cancer. This study set out to address that gap by examining the gene expression profiles of MECs located within invasive breast tumors and comparing them to MECs found in adjacent normal breast tissue.
A Transcriptomic View of Tumor-Associated MECs
The researchers analyzed archived breast cancer specimens from seven patients using GeoMx spatial transcriptomic profiling, a technology that enables detailed examination of gene activity within specific tissue regions. By isolating MECs from both tumor and adjacent normal areas, the team was able to identify significant differences in gene expression between the two populations.
Their analysis revealed 155 significantly dysregulated genes, including 129 that were upregulated and 26 that were downregulated in tumor-associated MECs. These findings suggest that MECs within invasive tumors undergo substantial molecular reprogramming.
Evidence of a Phenotypic Shift
One of the most striking findings was the increased expression of genes involved in extracellular matrix (ECM) remodeling and collagen production. Tumor-associated MECs showed elevated levels of multiple collagen genes, matrix metalloproteinases (MMP2, MMP9, MMP11, and MMP14), and ECM-associated proteins such as SPARC and lumican.
At the same time, these cells demonstrated reduced expression of traditional epithelial markers, including KRT5, KRT7, and KRT14. This combination of changes suggests a transition away from their normal barrier-forming role and toward a more mesenchymal, fibroblast-like phenotype that may contribute to tumor progression.
Remodeling the Tumor Microenvironment
The study's pathway analyses showed enrichment in biological processes related to:
- Extracellular matrix organization
- Collagen metabolism
- Integrin signaling
- Epithelial-mesenchymal transition (EMT)-associated pathways
These pathways are commonly associated with tissue remodeling, cell migration, and tumor invasion. The authors propose that MECs may help create a microenvironment that facilitates cancer cell movement and metastatic spread.
In addition to producing increased amounts of collagen, tumor-associated MECs expressed genes involved in growth factor signaling and angiogenesis, potentially supporting the development of new blood vessels and further promoting tumor progression.
Why These Findings Matter
For decades, myoepithelial cells have been viewed primarily as the breast's natural defense against cancer invasion. This study challenges that traditional perspective by demonstrating that MECs may be highly plastic and capable of adopting characteristics that support, rather than suppress, tumor development under certain conditions.
While additional research with larger patient cohorts is needed, these findings provide an important framework for understanding how changes within the tumor microenvironment influence breast cancer progression. They also highlight potential new avenues for future diagnostics and therapeutic strategies targeting the stromal components of breast tumors.
The findings from "Unraveling myoepithelial cell plasticity in breast cancer: a transcriptomic approach" offer a compelling look at how myoepithelial cells may transform during invasive breast cancer, shifting from a protective barrier to an active participant in tumor progression. By leveraging spatial transcriptomic technologies, the authors provide valuable insight into the dynamic relationship between cancer cells and their surrounding microenvironment. To read the full article, NSH members have access to the Journal of Histotechnology through their member dashboard. Simply log in to your dashboard and click "Journal of Histotechnology" to access current and archived content. Need a quick CEU? A quick quiz is also available with this article. You can take the quiz by going to eLearn and clicking Quizzes and JOH Tests. #2026#Blog#Multiomics,Assays,andMolecularApplications