Myoepithelial cells are specialized cells that sit at the boundary between glandular tissue and the surrounding stroma, combining properties of both epithelial cells and smooth muscle. They squeeze milk out of mammary glands, push saliva from salivary glands, and move sweat to the skin surface. Beyond contraction, they act as a living fence that helps prevent tumor cells from spreading into surrounding tissue, which makes their presence or absence a critical clue for pathologists trying to distinguish harmless breast lesions from invasive cancer.
A Cell With a Split Identity
Most cells in your body commit fully to one identity. Myoepithelial cells refuse. They simultaneously express proteins found in epithelial cells, such as cytokeratins and E-cadherin, and proteins normally reserved for smooth muscle, including smooth muscle alpha-actin, calponin, and smooth muscle myosin heavy chains.1PubMed. Expression of smooth muscle-specific proteins in myoepithelium and stromal myofibroblasts of normal and malignant human breast tissue This dual nature gives them the ability to contract like muscle while remaining structurally integrated into glandular epithelium. Under the electron microscope, their interiors are packed with contractile filaments arranged in patterns that resemble those seen in striated muscle.2PubMed Central. Fine structure of the myoepithelium of the eccrine sweat glands of man
Myoepithelial cells can also shift their appearance depending on what the tissue needs. Researchers studying the mammary gland have described at least four morphological types, ranging from flat, immobile cells tightly attached to the basement membrane to elongated, motile forms that resemble fibroblasts. As cells transition from the stationary type to the motile type, they gradually lose their epithelial markers and begin expressing mesenchymal ones like vimentin.3PubMed Central. Morphology of the myoepithelial cell: immunohistochemical characterization from resting to motile phase This shape-shifting capacity makes them unusually adaptable, but it also creates headaches for pathologists trying to identify them in tissue samples.
Where They Live
Myoepithelial cells are found wherever the body needs to physically squeeze secretions out of glandular tissue. Their most studied home is the breast, where they form a continuous outer layer wrapped around the branching ductal system. An inner layer of luminal cells produces milk, while the myoepithelial layer sits just outside, resting on the basement membrane.4PubMed Central. Myoepithelial cells: their origin and function in breast morphogenesis and neoplasia The shape of these cells changes across the breast’s architecture. Along the ducts, they tend to be spindle-shaped and oriented lengthwise. During pregnancy and lactation, the cells around the milk-producing lobules enlarge dramatically into star-shaped forms, their branching arms interlacing to form a basket-like grip around each swollen alveolus.5PubMed. Cell size and shape changes in the myoepithelium of the mammary gland during differentiation
Salivary glands are another major location. Both major salivary glands (parotid, submandibular, sublingual) and the smaller minor salivary glands scattered throughout the mouth contain myoepithelial cells that wrap around secretory units. These cells closely resemble their breast counterparts, expressing many of the same markers, though the range of tumor types that arise from salivary myoepithelial cells is broader and sometimes more diagnostically challenging.6PubMed Central. Pathophysiology of myoepithelial cells in salivary glands
Eccrine sweat glands, the type responsible for temperature regulation across most of the skin, also depend on myoepithelial cells. In the coiled secretory portion buried deep in the dermis, these cells align obliquely along the tubule and contract in coordinated waves, generating the peristaltic motion that pushes sweat up toward the skin surface.7PubMed Central. Gap junction-mediated contraction of myoepithelial cells induces the peristaltic transport of sweat in human eccrine glands Live three-dimensional imaging has shown that sweat-gland myoepithelial cells are distinguishable from the cuboidal luminal cells by their elongated shape and elliptical nuclei.8Nature. Gap junction-mediated contraction of myoepithelial cells induces the peristaltic transport of sweat in human eccrine glands
Less commonly discussed are the myoepithelial cells in bronchial submucosal glands, the glands lining the airways that produce mucus. These cells normally play a quiet supporting role, but in fatal asthma they have been found to undergo significant enlargement. Compared with the airways of people without asthma, the myoepithelial cell area in fatal asthma cases was disproportionately increased relative to total gland size, and electron microscopy revealed that the cells were packed with extra contractile filaments.9PubMed. Increased myoepithelial cells of bronchial submucosal glands in fatal asthma Whether this hypertrophy contributes to the deadly mucus plugging seen in severe asthma or is a compensatory response remains an open question.
How They Contract
The best-understood contraction job belongs to mammary myoepithelial cells during breastfeeding. When a baby suckles, the brain releases oxytocin from the posterior pituitary gland. Oxytocin circulates through the blood to the breast, where it binds to receptors on myoepithelial cells.10PubMed Central. Physiological and pharmacological evaluation of oxytocin-induced milk ejection in mice The cells then squeeze the milk-filled alveoli, ejecting milk into the ductal system and out through the nipple. Mouse experiments have confirmed that this contraction depends on smooth muscle alpha-actin: when the gene encoding this protein was knocked out, mammary myoepithelial cells lost their contractile force and milk ejection failed.11PubMed Central. Myoepithelial cell contraction and milk ejection are impaired in mammary glands of mice lacking smooth muscle alpha-actin
In salivary glands, the signaling is different but the outcome is similar. Parasympathetic nerves release acetylcholine, which binds to muscarinic receptors on myoepithelial cells and triggers contraction of the acini, helping to push saliva into the duct system.12PubMed. A parasympathetic neurotransmitter induces myoepithelial cell differentiation during salivary gland development Work in dogs showed that sympathetic nerves also contribute, and that the two branches of the autonomic nervous system actually work together synergistically: simultaneous parasympathetic and sympathetic stimulation produced stronger myoepithelial contraction than either signal alone. The sympathetic component operates through alpha-1 adrenergic receptors.13PubMed Central. Autonomic nervous control of myoepithelial cells and secretion in submandibular gland of anaesthetized dogs
In eccrine sweat glands, the coordination is even more elegant. Myoepithelial cells communicate with each other through gap junctions, allowing them to contract in rhythmic waves rather than all at once. This produces peristaltic pumping, much like the motion of the intestines, which efficiently pushes sweat along the coiled tubule and up to the skin surface.7PubMed Central. Gap junction-mediated contraction of myoepithelial cells induces the peristaltic transport of sweat in human eccrine glands
The Tumor-Suppressing Fence
Beyond contraction, the myoepithelial layer acts as a structural and biochemical barrier against cancer progression. In the breast, myoepithelial cells form a semi-continuous sheet that physically separates the epithelium from the surrounding stroma, and they actively secrete factors that inhibit tumor invasion and new blood vessel formation.14PubMed Central. Role of myoepithelial cells in breast tumor progression Think of them as both a wall and an alarm system: they maintain the basement membrane, help keep luminal cells properly oriented, and release proteins that directly suppress the ability of cancer cells to spread.
The list of tumor-suppressing activities is long. Myoepithelial cells produce proteinase inhibitors that block the enzymes cancer cells use to chew through tissue barriers. They secrete anti-angiogenic factors that starve tumors of new blood supply. And they maintain the structural polarity of the luminal layer, which is itself a check on malignant behavior. Disruption of the myoepithelial layer has been shown to facilitate invasion of cancer cells into surrounding stroma.15PubMed Central. Re-evaluation of the myoepithelial cells roles in the breast cancer progression
This tumor-suppressive role is exactly why pathologists pay so much attention to the myoepithelial layer when evaluating breast biopsies. A lesion surrounded by an intact myoepithelial layer is still contained: it has not yet invaded through the boundary. A lesion lacking that layer has broken through, and the clinical implications shift dramatically.
Identifying Myoepithelial Cells Under the Microscope
Pathologists rely on immunohistochemical stains to detect myoepithelial cells in tissue samples, and the choice of marker matters. The most commonly used stain targets smooth muscle actin, which is sensitive and reliable but has an annoying weakness: it also lights up stromal fibroblasts and blood vessel walls, creating potential confusion in crowded tissue fields.16PubMed. The usefulness of p63 as a marker of breast myoepithelial cells
The nuclear protein p63 has become a favored alternative. Because p63 stains only the nucleus, the signal is easy to read even in dense or cytologically complex preparations. It does not react with fibroblasts or vascular smooth muscle, solving the specificity problem of actin-based stains. In one study comparing p63 to calponin and smooth muscle myosin heavy chain across 85 breast lesions, none of the cases showed p63 staining in myofibroblasts, while calponin cross-reacted with myofibroblasts in over three-quarters of cases.17PubMed. Immunohistochemical distinction of invasive from noninvasive breast lesions: a comparative study of p63 versus calponin and smooth muscle myosin heavy chain However, p63 is not perfect. It occasionally shows a discontinuous-looking myoepithelial layer around certain in situ carcinomas, and a small fraction of actual breast cancer cells express p63, which could theoretically cause a false impression that an invasive tumor retains its myoepithelial lining.
In practice, pathologists often use a panel of two or more markers to compensate for each one’s blind spots. Research tracking the progressive loss of myoepithelial markers around breast ducts involved by ductal carcinoma in situ found that p63 disappears first, followed by calponin, and then smooth muscle actin drops off last.18PubMed Central. Myoepithelial cell differentiation markers in ductal carcinoma in situ progression This ordered loss pattern is clinically useful: a duct that has lost p63 but still shows actin staining may be at an earlier stage of myoepithelial compromise than one that has lost all three markers.
Myoepithelial Tumors
Although myoepithelial cells normally act as tumor suppressors, they can themselves become malignant. Myoepithelial carcinoma is rare, and most cases originate in salivary glands, particularly the parotid. In a study of 17 patients with myoepithelial-cell-rich tumors, the parotid was the primary site in the majority, with the submandibular and minor salivary glands accounting for most of the remainder.19PubMed. Myoepithelial cell-rich neoplasms: cytologic features of benign and malignant lesions Benign versions also exist, typically presenting as pleomorphic adenomas, which are the most common salivary gland tumors overall.
Myoepithelial carcinoma carries a significant risk of distant spread. A clinicopathologic study of 48 cases found that about a quarter of patients developed distant metastases, with the lung as the most frequent destination. Roughly half of the carcinomas arose de novo, while the other half developed within a pre-existing pleomorphic adenoma, a scenario called carcinoma ex-pleomorphic adenoma. The latter group had worse outcomes. Tumor necrosis turned out to be the most informative prognostic feature: no distant recurrence was observed among patients whose tumors lacked necrosis over a median follow-up of nearly four years.20PubMed Central. Prognostic factors in myoepithelial carcinoma of salivary glands: a clinicopathologic study of 48 cases
A separate series of 23 myoepithelial carcinomas of the head and neck reported five-year overall survival around 32% and five-year progression-free survival around 31%. Local relapse occurred in roughly a third of patients, and distant metastases again favored the lungs and, in some cases, the brain. Most recurrences happened within the first three years.21Cancer Treatment Communications. Myoepithelial carcinoma of the head and neck: A report of 23 cases and literature review
Epithelial-Myoepithelial Carcinoma and Its Look-Alikes
Epithelial-myoepithelial carcinoma (EMC) is a distinct low-grade salivary gland tumor built from two cell types: an inner layer of duct-lining epithelial cells and an outer cuff of large, clear myoepithelial cells. It is a less aggressive tumor overall than pure myoepithelial carcinoma, but it has a diagnostic trap. Some EMCs develop regions that look very similar to adenoid cystic carcinoma (AdCC), a much more aggressive cancer with high rates of nerve invasion, distant spread, and poor long-term survival. Mistaking EMC for AdCC on a needle biopsy could lead to unnecessarily aggressive surgery, while the reverse error could lead to undertreatment.22American Journal of Clinical Pathology. Fine-Needle Aspiration of Epithelial-Myoepithelial Carcinoma of the Parotid Gland With Prominent Adenoid Cystic Carcinoma–Like Cribriform Features: Avoiding a Diagnostic Pitfall
Molecular studies have helped clarify this overlap. Fusions of the MYB gene are a hallmark of AdCC but were not found in any of the classic, low-grade EMCs tested in one study. However, EMC variants that showed hybrid features with AdCC or a highly infiltrative growth pattern were significantly more likely to harbor MYB fusions, suggesting that some of these “EMCs” may actually be AdCCs in disguise.23PubMed Central. MYB Translocation Status in Salivary Gland Epithelial-Myoepithelial Carcinoma: Evaluation of Classic, Variant, and Hybrid Forms For the pathologist, checking for a MYB gene rearrangement has become a practical way to sort these ambiguous cases.
Myoepithelial Cells as Reserve Stem Cells
One of the more surprising discoveries about myoepithelial cells is that they can function as reserve stem cells. In the mouse trachea, myoepithelial cells normally sit quietly in the submucosal glands. But after severe airway injury, lineage-tracing experiments showed that these cells activated, migrated to the damaged surface epithelium, adopted a basal cell identity, and gave rise to at least seven different airway cell types. They also established lasting progenitor populations capable of responding to a second round of injury.24PubMed Central. Submucosal Gland Myoepithelial Cells Are Reserve Stem Cells That Can Regenerate Mouse Tracheal Epithelium
Sweat glands show a parallel story. Slowly dividing label-retaining cells with myoepithelial characteristics were identified in the proximal region of sweat glands. Under injury conditions, these cells divided and contributed to the regeneration of the overlying epidermis.25PLOS ONE. Label Retaining Cells (LRCs) with Myoepithelial Characteristic from the Proximal Acinar Region Define Stem Cells in the Sweat Gland This regenerative capacity is of interest for wound healing research and tissue engineering, since sweat glands are among the few appendages that survive deep burns and could theoretically serve as a reservoir for skin repair.
Changes During Tissue Remodeling
Myoepithelial cells are not static structures. Even in normal physiology, they remodel themselves extensively. During mammary gland involution, the process by which the breast returns to its pre-lactation state after weaning, three-dimensional imaging has revealed that myoepithelial cells undergo distinct morphological changes as the tissue regresses. These shape shifts were not visible in traditional flat tissue sections and only became apparent when researchers could view the cells in their full three-dimensional context.26PubMed Central. Dynamic architectural interplay between leucocytes and mammary epithelial cells The remodeling appears to help coordinate the orderly dismantling of milk-producing structures, working alongside immune cells that clear away dead cells and excess tissue.
This dynamic behavior fits with the broader picture of myoepithelial cells as active participants in tissue architecture rather than passive scaffolding. They help build the basement membrane, reshape it during development, and participate in its controlled breakdown when the tissue no longer needs it. In the breast, the period of lactation and involution may be the most dramatic example of this remodeling cycle, with myoepithelial cells morphing from expansive star-shaped contractile cells back toward their resting spindle shapes as the gland quiets down.
Myoepithelial Cells in Triple-Negative Breast Cancer
The behavior of myoepithelial cells in the tumor microenvironment is a growing area of research, particularly in triple-negative breast cancer (TNBC), the subtype that lacks estrogen, progesterone, and HER2 receptors and tends to be more aggressive. Single-cell sequencing studies have found that myoepithelial cells associated with TNBC show increased expression of proliferation- and immune-related genes while decreasing their expression of inflammatory and extracellular-matrix-related genes.27PubMed Central. Decoding the Tumor Microenvironment of Myoepithelial Cells in Triple-Negative Breast Cancer Through Single-Cell and Transcriptomic Sequencing and Establishing a Prognostic Model Based on Key Myoepithelial Cell Genes In other words, the tumor seems to alter the gene-expression profile of the myoepithelial cells around it, potentially weakening their protective barrier function. Understanding how cancer co-opts or degrades the myoepithelial fence is one of the more active frontiers in breast cancer biology, and the gene signatures being identified in these studies may eventually feed into prognostic models or therapeutic targets.
Research into the mechanical forces at play during collective tumor invasion has added another layer. In breast cancer organoid models, basal-like cells that share certain features with myoepithelial cells were found to act as invasion leaders, driving clusters of tumor cells into surrounding tissue. A mechanotransduction loop involving the protein YAP was required for this behavior: blocking YAP activity reduced collective invasion by at least 45% in patient-derived breast cancer organoids without affecting cell proliferation.28Nature Communications. A YAP-centered mechanotransduction loop drives collective breast cancer cell invasion This finding suggests that the same contractile and mechanical signaling properties that make myoepithelial cells such effective protectors in healthy tissue can be hijacked by cancer cells to facilitate spread when the normal regulatory context breaks down.