Establishment and characterization of immortalized sweat gland myoepithelial cells

Sweat glands play an important role in thermoregulation via sweating, and protect human vitals. The reduction in sweating may increase the incidence of hyperthermia. Myoepithelial cells in sweat glands exhibit stemness characteristics and play a major role in sweat gland homeostasis and sweating processes. Previously, we successfully passaged primary myoepithelial cells in spheroid culture systems; however, they could not be maintained for long under in vitro conditions. No myoepithelial cell line has been established to date. In this study, we transduced two immortalizing genes into primary myoepithelial cells and developed a myoepithelial cell line. When compared with primary sweat gland cells, the immortalized myoepithelial cells (designated "iEM") continued to form spheroids after the 4th passage and expressed α-smooth muscle actin and other proteins that characterize myoepithelial cells. Furthermore, treatment with small compounds targeting the Wnt signaling pathways induced differentiation of iEM cells into luminal cells. Thus, we successfully developed an immortalized myoepithelial cell line having differentiation potential. As animal models are not useful for studying human sweat glands, our cell line will be helpful for studying the mechanisms underlying the pathophysiology of sweating disorders.

Biphasic Sarcomatoid Sweat Gland Carcinoma With Ductal Epithelial And Spindled Myoepithelial Cell Components (Malignant Mixed Tumor Of Skin)

Introduction/Objective Sweat gland carcinomas are a group of malignant skin adnexal tumors that are difficult to diagnose due to their rarity, wide morphologic variation, and limited literature on diagnosis and classification. These tumors may appear bland and morphologically resemble benign skin adnexal tumors, or may appear poorly differentiated and mimic metastatic carcinoma especially from a breast primary. Biphasic sweat gland carcinomas are an even rarer entity, with only few cases reported in literature, and have been described to consist of a well- differentiated ductal epithelial component and a poorly differentiated, sarcomatoid, spindle cell component. Methods/Case Report Our case report describes a 53 year old female referred to our institution for diagnosis of an excised skin lesion of the right upper arm, which had been slowly growing for 8 years. The histology revealed a biphasic malignant neoplasm involving the dermis and subcutis. The tumor consisted of an epithelial cell component with glandular and squamoid morphology and positive for CK5/6, CK7, and CAM5.2, and a spindled myoepithelial cell component with sarcomatoid morphology and positive for S100, vimentin, and p63. Stains for CK20, ER, PR, PAX8, CEA, and TTF1 were negative. The histological and clinical findings favored a primary skin adnexal tumor, rather than a metastatic lesion. The patient underwent wide local excision of the lesion given that margins of the original excision were indeterminate. The histology of this re-excision demonstrated the same biphasic tumor with ductal epithelial and sarcomatoid myoepithelial cell components positive for the same stains. Although margins were negative in this re-excision, 3-4 months later, the patient developed dyspnea with multiple new pulmonary and hilar masses discovered on imaging, and new-onset headache with a frontal lobe mass discovered on brain imaging. These masses were biopsied/resected, and revealed to be metastases of the original cutaneous tumor positive for the same markers. Results (if a Case Study enter NA) NA Conclusion This case report describes a rare, diagnostically challenging case of a biphasic sweat gland carcinoma with ductal epithelial and sarcomatoid myoepithelial cell components, which demonstrated aggressive behavior with distant metastasis. These tumors are a clinicopathological quandary given their rarity and the paucity of literature on their characterization.

High-content siRNA 3D co-cultures to identify myoepithelial cell-derived breast cancer suppressor proteins

Understanding how cancer cells interact with the surrounding microenvironment early in breast cancer development can provide insight into the initiation and progression of invasive breast cancers. The myoepithelial cell layer surrounding breast ducts acts as a physical barrier in early breast cancer, preventing cancer cells from invading the surrounding stroma. Changes to the expression profile and properties of myoepithelial cells have been implicated in progression to invasive carcinoma. Identifying the molecular drivers of myoepithelial cell-mediated tumour suppression may offer new approaches to predict and block the earliest stages of cancer invasion. We employed a high-content approach to knock down 87 different genes using siRNA in an immortalised myoepithelial cell line, prior to co-culture with invasive breast cancer cells in 3D. Combined with high-content imaging and a customised analysis pipeline, this system was used to identify myoepithelial proteins that are necessary to control cancer cell invasion. This dataset has identified prospective myoepithelial suppressors of early breast cancer invasion which may be used by researchers to investigate their clinical validity and utility.

Impact of estrogen population pharmacokinetics on a QSP model of mammary stem cell differentiation into myoepithelial cells

<abstract> <p>Stem cell differentiation cascades are critical components of healthy tissue maintenance. Dysregulation in these systems can lead to serious diseases, including cancer. Myoepithelial mammary cells are produced from differentiated mammary stem cells in processes regulated, in part, by estrogen signalling and concentrations. To quantify and predict the production of mammary myoepithelial cell production by estrogen, we developed a mechanistic, quantitative systems pharmacology (QSP) model that includes the explicit characterization of free and unbound estrogen concentrations in circulation. Linking this model to a previously developed population pharmacokinetics model for ethinyl estradiol, a synthetic form of estrogen included in oral contraceptives, we predicted the effects of estrogen on myoepithelial cell development. Interestingly, pharmacokinetic intraindividual variability alone did not significantly impact on our modelos predictions, suggesting that combinations of physiological and pharmacokinetic variability drive heterogeneity in mechanistic QSP models. Our model is one component of an improved understanding of mammary myoepithelial cell production and development, and our results support the call for mechanistically constructed systems models for disease and pharmaceutical modelling.</p> </abstract>

Mixed Invasive Apocrine Papillary/Micropapillary Carcinoma of the Breast: Another Brick in the Triple-Negative Wall

Pure invasive papillary carcinoma (IPC) is a rare subtype of breast carcinoma with good prognosis compared with classical invasive breast carcinoma (IBC) of no special type. The majority of IPC are estrogen receptor and progesterone receptor (ER/PR) positive and HER2 negative (luminal A-like). We report the case of a 72-year-old women who was referred to the Senology Clinic for a routine workup following surgery for an intraductal papilloma. The core needle biopsy (CNB) showed a lesion mainly composed of irregular papillae and micropapillae with apocrine epithelial cells of low-to-intermediate nuclear grade, without a myoepithelial cell layer within the papillae and at the periphery, as demonstrated with multiple immunostains. The diagnosis of apocrine papillary lesion of uncertain malignant potential was made. The subsequent lumpectomy showed an IBC with the same cyto-architectural features as the CNB. In addition, lymphovascular invasion and papillary/micropapillary apocrine in situ lesion were noted. Notably, the tumor was ER/PR and HER2 negative and strongly positive for androgen receptor. A final diagnosis of mixed apocrine papillary/micropapillary carcinoma with triple-negative status was made. To the best of our knowledge, this is the first report of an IBC with these features. Breast pathologists should be aware of this entity when dealing with CNB samples characterized by a complex papillary lesion with apocrine atypia that lacks a myoepithelial cell layer on multiple immunostains. These lesions should be classified at least as of uncertain malignant potential based on the cyto-architectural features prompting a surgery for removal.