FGF-2, TGFβ-1, PDGF-A and respective receptors expression in pleomorphic adenoma myoepithelial cells: an in vivo and in vitro study

Abstract

Myoepithelial cells have an important role in salivary gland tumor development, contributing to a low grade of aggressiveness of these tumors. Normal myoepithelial cells are known by their suppressor function presenting increased expression of extracellular matrix genes and protease inhibitors. The importance of stromal cells and growth factors during tumor initiation and progression has been highlighted by recent literature. Many tumors result from the alteration of paracrine growth factors pathways. Growth factors mediate a wide variety of biological processes such as development, tissue repair and tumorigenesis, and also contribute to cellular proliferation and transformation in neoplastic cells.ObjectivesThis study evaluated the expression of fibroblast growth factor-2 (FGF-2), transforming growth factor β-1 (TGFβ-1), platelet-derived growth factor-A (PDGF-A) and their respective receptors (FGFR-1, FGFR-2, TGFβR-II and PDGFR-α) in myoepithelial cells from pleomorphic adenomas (PA) by in vivo and in vitro experiments.Material and MethodsSerial sections were obtained from paraffin-embedded PA samples obtained from the school’s files. Myoepithelial cells were obtained from explants of PA tumors provided by surgery from different donors. Immunohistochemistry, cell culture and immunofluorescence assays were used to evaluate growth factor expression.ResultsThe present findings demonstrated that myoepithelial cells from PA were mainly positive to FGF-2 and FGFR-1 by immunohistochemistry and immunofluorescence. PDGF-A and PDGFR-α had moderate expression by immunohistochemistry and presented punctated deposits throughout cytoplasm of myoepithelial cells. FGFR-2, TGFβ-1 and TGFβR-II were negative in all samples.ConclusionsThese data suggested that FGF-2 compared to the other studied growth factors has an important role in PA benign myoepithelial cells, probably contributing to proliferation of these cells through the FGFR-1.

The increased PDGF-A, PDGF-B and FGF-2 expression in recurrence of salivary gland pleomorphic adenoma

“…Among these, families of the platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) have been shown to have an important role in the pathogenesis and progression of different tumours types, including salivary gland tumours 7–9. FGF-2 has been implicated as having an important role in myoepithelial cell proliferation mediated by the FGFR-1 receptor in PA 8. Moreover, it has been shown that cells from carcinoma ex-pleomorphic adenoma (CXPA) have increased expression of EGFR, FGF-2, FGFR-1, FGFR-2, HFG-A, c-Met, TGF-β1, TGFBR-II and IGFR-1 in comparison with ductal epithelial PA cells 9.…”

The role of FGF-2/HGF and fibronectin matrix on pleomorphic adenoma myoepithelial cell morphology and immunophenotype: anin vitrostudy

“…FGF-2 is an important growth factor, which is involved the biological behavior of salivary gland tumors Miguita et al, 2010). Miguita et al (2010) showed that FGF-2 and its receptor (FGFR-1) are expressed in myoepithelial cells from PA, suggesting that FGF-2 may have an important autocrine role on the biological behavior of myoepithelial cells, mediated by the FGFR-1 receptor.…”

“…FGF-2 is an important growth factor, which is involved the biological behavior of salivary gland tumors Miguita et al, 2010). Miguita et al (2010) showed that FGF-2 and its receptor (FGFR-1) are expressed in myoepithelial cells from PA, suggesting that FGF-2 may have an important autocrine role on the biological behavior of myoepithelial cells, mediated by the FGFR-1 receptor. Furthermore, Martinez et al (2010) demonstrated that the FGF-2 expression in myoepithelial cells was increased by stimulation via the conditioned medium from malignant cells, indicating a paracrine myoepithelial/epithelial cell interaction that could favor tumor growth, invasion and metastasis.…”

“…Validation of results was achieved via cell culture replicates obtained from three different donors, as per described in a previous study Miguita et al, 2010). This study was conducted following the approval of the Ethical Committee of São Leopoldo Mandic Institute and Research Center, Campinas, Brazil (Protocol Nos 12/0053 and 12/0064).…”

Could a Possible Crosstalk between AMPK and TGF-β Signaling Pathways Be a Key Player in Benign and Malignant Salivary Gland Tumors?

“…LKB1 and SMAD4havebeeninspectedincommonhumantumors,but their possible crosstalk and involvement in EMT and tumor heterogeneityhasnotbeenstudiedtodate [11,16,17].There is no literature to connect LKB1 deficiency with human SGTs,butsomaticmutationhasbeenreportedtobeacurrent event in human lung cancer, suggesting a tumor-suppressive roleinepithelialtissues [18].Also,theTGF-βsignalingpath-way contains crucial tumorgenesis mediators like SMAD4 which play a role in the initiation and progression of many human tumors and EMT [16,19]. Its deficiency promotes β-cateninaccumulationandepithelialcelldifferentiationand proliferation [11].Apluripotentstemcellgroupisresponsible fortheheterogeneityreportedwithinSGTs;however,based on recent data, the histomorphological heterogeneity could also be related to all the mature cell types in salivary gland tissues [20].Whenoncogenesisoccurs,thelevelofdifferentiationofthereservecell'sdescendantsdeterminestheheterogeneity of the SGTs and their mesenchymal differentiation affectingtheresultsofgeneexpressionassays [21].…”