Two sides of the same coin: Insights into the myoepithelial cells in carcinoma ex pleomorphic adenoma development

Scarini, João Figueira; Egal, Érika Said Abu; Lima‐Souza, Reydson Alcides de; Crescencio, Lívia Ramalho; Emerick, Carolina; Kowalski, Luiz Paulo; Altemani, Albina; Mariano, Fernanda Viviane

doi:10.1016/j.critrevonc.2020.103195

Cited by 7 publications

(10 citation statements)

References 49 publications

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“…Tenascin expression is absent in the malignant ductal epithelial cells of the CXPA while a strong and diffuse positivity is present in the cytoplasm of the CXPA malignant myoepithelial cells (69). These findings indicate the importance of tenascin as a contributor to the myoepithelial cell-promoting potential in the CXPA (11). Indeed, a key promoting role of tenascin in the CXPA progression was evidenced in the study by Félix and collaborators (2004) where all cases of CXPA presenting positivity for tenascin showed metastases at some point during the follow-up period (70) (Table 1).…”

Section: Mmps and Timpsmentioning

confidence: 83%

“…The myoepithelial cell in the autophagy/senescence process may produce metabolites that would be used as energy by the epithelial cells. The epithelial cells may break the basement membrane and invade the adjacent tissues ( 96 , 11 ).…”

Section: Ecm In Pa-cxpa Progressionmentioning

confidence: 99%

“…Most of them affect the parotid glands, usually manifesting in adult women between 50 and 70 years old ( 5 , 7 ). Recent studies showed that genomic instability ( 8 , 9 ), metabolic shifts ( 10 ), and changes in the tumor microenvironment (TME), mainly governed by the myoepithelial cell ( 11 ), are the most important molecular events oin the CXPA carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

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Heterogeneity and versatility of the extracellular matrix during the transition from pleomorphic adenoma to carcinoma ex pleomorphic adenoma: cumulative findings from basic research and new insights

Scarini

Lima‐Souza

Lavareze

et al. 2023

Front. Oral. Health

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Pleomorphic adenoma (PA) is the most common salivary gland tumor, accounting for 50%–60% of these neoplasms. If untreated, 6.2% of PA may undergo malignant transformation to carcinoma ex-pleomorphic adenoma (CXPA). CXPA is a rare and aggressive malignant tumor, whose prevalence represents approximately 3%–6% of all salivary gland tumors. Although the pathogenesis of the PA-CXPA transition remains unclear, CXPA development requires the participation of cellular components and the tumor microenvironment for its progression. The extracellular matrix (ECM) comprises a heterogeneous and versatile network of macromolecules synthesized and secreted by embryonic cells. In the PA-CXPA sequence, ECM is formed by a variety of components including collagen, elastin, fibronectin, laminins, glycosaminoglycans, proteoglycans, and other glycoproteins, mainly secreted by epithelial cells, myoepithelial cells, cancer-associated fibroblasts, immune cells, and endothelial cells. Like in other tumors including breast cancer, ECM changes play an important role in the PA-CXPA sequence. This review summarizes what is currently known about the role of ECM during CXPA development.

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Section: Mmps and Timpsmentioning

confidence: 83%

Section: Ecm In Pa-cxpa Progressionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Heterogeneity and versatility of the extracellular matrix during the transition from pleomorphic adenoma to carcinoma ex pleomorphic adenoma: cumulative findings from basic research and new insights

Scarini

Lima‐Souza

Lavareze

et al. 2023

Front. Oral. Health

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“…Otras funciones incluyen acciones como receptores sensoriales y la producción de componentes de la membrana basal y la matriz extracelular (Rao et al, 2014). Según Figueira Scarini et al (2021) los mioepiteliocitos tienen además un papel supresor tumoral.…”

Section: Discussionunclassified

Carcinoma Mioepitelial Ex-Adenoma Pleomórfico de Glándula Parótida: Reporte de un Caso y Análisis Inmunohistoquímico

Samar-Romani¹,

Avila-Uliarte²,

Corball-de-Santiago³

et al. 2022

Int. J. Odontostomat.

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RESUMEN:El carcinoma mioepitelial es una rara neoplasia maligna de las glándulas salivales; puede originarse de novo o desarrollarse en un adenoma pleomórfico preexistente o un mioepitelioma. Las características histológicas e inmunohistoquímicas de un caso de carcinoma mioepitelial de glándula parótida originado por la transformación maligna de un adenoma pleomórfico primario previo se investigaron en este trabajo. Se demostró la presencia de mitosis, pleomorfismo nuclear, áreas necróticas, mioepiteliocitos con una marcación con p63 superior al 75 % y un índice proliferativo de 15 %, características que pueden desencadenar un desenlace adverso. Resulta clave el examen periódico de la paciente que dará una probabilidad superior de curación y sobrevida y de investigar eventuales recurrencias o metástasis.

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“…Liotta et al postulated that the malignant transformation of a tumour reflects the ability of neoplastic cells to overcome growth restrictions in the tumour microenvironment (TME) [ 11 ]. Scarini et al propose that during CXPA carcinogenesis, several molecular signals from TME may induce malignant transformation of benign PA cells [ 12 ]. For instance, tenascin, an extracellular matrix (ECM) glycoprotein, was found to be expressed in the stroma of CXPA, which may contribute to neoplastic proliferation [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Extracellular matrix remodelling and stiffening contributes to tumorigenesis of salivary carcinoma ex pleomorphic adenoma——A study based on patient-derived organoids

Chen

et al. 2023

Cell Biosci

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Background Salivary carcinoma ex pleomorphic adenoma (CXPA) is defined as a carcinoma that develops from benign pleomorphic adenoma (PA). Abnormally activated Androgen signaling pathway and amplification of HER-2/neu(ERBB-2) gene are known to be involved in CXPA tumorigenesis. Recent progress in tumour microenvironment research has led to identification that extracellular matrix (ECM) remodelling and increased stiffness act as critical contributing role in tumour carcinogenesis. This study examined ECM modifications to elucidate the mechanism underlying CXPA tumorigenesis. Results PA and CXPA organoids were successfully established. Histological observation, immunohistochemistry (IHC), and whole-exome sequencing demonstrated that organoids recapitulated phenotypic and molecular characteristics of their parental tumours. RNA-sequencing and bioinformatic analysis of organoids showed that differentially expressed genes are highly enriched in ECM-associated terms, implying that ECM alternations may be involved in carcinogenesis. Microscopical examination for surgical samples revealed that excessive hyalinized tissues were deposited in tumour during CXPA tumorigenesis. Transmission electron microscopy confirmed that these hyalinized tissues were tumour ECM in nature. Subsequently, examination by picrosirius red staining, liquid chromatography with tandem mass spectrometry, and cross-linking analysis indicated that tumour ECM was predominantly composed of type I collagen fibers, with dense collagen alignment and an increased level of collagen cross-linking. IHC revealed the overexpression of COL1A1 protein and collagen-synthesis-related genes, DCN and IGFBP5 (p < 0.05). Higher stiffness of CXPA than PA was demonstrated by atomic force microscopy and elastic imaging analysis. We utilized hydrogels to mimic ECM with varying stiffness degrees in vitro. Compared with softer matrices (5Kpa), CXPA cell line and PA primary cells exhibited more proliferative and invasive phenotypes in stiffer matrices (50Kpa, p < 0.01). Protein-protein interaction (PPI) analysis of RNA-sequencing data revealed that AR and ERBB-2 expression was associated with TWIST1. Moreover, surgical specimens demonstrated a higher TWIST1 expression in CXPA over PA. After knocking down TWIST1 in CXPA cells, cell proliferation, migration, and invasiveness were significantly inhibited (p < 0.01). Conclusion Developing CXPA organoids provides a useful model for cancer biology research and drug screening. ECM remodelling, attributed to overproduction of collagen, alternation of collagen alignment, and increased cross-linking, leads to increased ECM stiffness. ECM modification is an important contributor in CXPA tumorigenesis.

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Two sides of the same coin: Insights into the myoepithelial cells in carcinoma ex pleomorphic adenoma development

Cited by 7 publications

References 49 publications

Heterogeneity and versatility of the extracellular matrix during the transition from pleomorphic adenoma to carcinoma ex pleomorphic adenoma: cumulative findings from basic research and new insights

Heterogeneity and versatility of the extracellular matrix during the transition from pleomorphic adenoma to carcinoma ex pleomorphic adenoma: cumulative findings from basic research and new insights

Carcinoma Mioepitelial Ex-Adenoma Pleomórfico de Glándula Parótida: Reporte de un Caso y Análisis Inmunohistoquímico

Extracellular matrix remodelling and stiffening contributes to tumorigenesis of salivary carcinoma ex pleomorphic adenoma——A study based on patient-derived organoids

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