Fibrillin-1, a novel TGF-beta-induced factor, is preferentially expressed in metaplastic carcinoma with spindle sarcomatous metaplasia
Journal
Pathology
Journal Volume
51
Journal Issue
4
Pages
375-383
Date Issued
2019
Author(s)
Abstract
TGF-β induces epithelial–mesenchymal transition (EMT), which is involved in tumour progression. This study aims to identify and characterise novel factors potentially related to TGF-β-mediated tumour aggression in breast cancer. We treated the human mammary epithelial cell line MCF10A with TGF-β and observed TGF-β-dependent upregulation of FBN1, involving demethylation of CpG sites, in MCF10A cells undergoing EMT. The biological importance of fibrillin-1, encoded by FBN1, was evaluated through immunohistochemistry on 225 breast cancer specimens of various subtypes. Fibrillin-1 expression was observed only in metaplastic carcinoma of the breast (MCB) (51.7%), and the expression was observed in spindle sarcomatous metaplasia (SSM), but not in other metaplasia, including matrix-producing, pleomorphic, and squamous metaplasia, and carcinomatous components of both MCB and non-MCB. Fibrillin-1 expression was also restricted to the SSM of non-mammary carcinosarcomas of various organs. Overall, fibrillin-1 expression was enriched in MCB and non-mammary carcinosarcoma with SSM (93.7% and 93.3%, respectively), but not in MCBs and non-mammary carcinosarcoma without SSM. FBN1 knockdown in MDA-MB-231 cells with high FBN1 expression did not compromise migration, invasion, and tumourigenesis, and did not alter the expression of other EMT-related markers. In conclusion, fibrillin-1 is a novel TGF-β-induced marker. Fibrillin-1 expression in SSM, but not in other metaplasia and carcinomatous components, in both MCBs and non-mammary carcinosarcomas, together with the inability of FBN1-knockdown to compromise migration and invasion, indicates that fibrillin-1 is a marker induced solely in spindle metaplasia during EMT and does not induce EMT nor lead to tumour aggressiveness. ? 2019 Royal College of Pathologists of Australasia
Subjects
breast; epithelial-mesenchymal transition; fibrillin-1; metaplastic carcinoma; TGF-β
SDGs
Other Subjects
cdh2 protein; fibrillin 1; fn protein; mitogen activated protein kinase 1; mitogen activated protein kinase 3; protein; protein kinase B; snai1 protein; stress activated protein kinase; synaptophysin; transcription factor Slug; transcription factor ZEB1; Twist related protein 1; unclassified drug; uvomorulin; vim protein; vimentin; fibrillin 1; transforming growth factor beta; Article; breast carcinoma; breast epithelium cell; cancer growth; carcinogenesis; carcinosarcoma; cell invasion; cell migration; controlled study; DNA demethylation; down regulation; gene expression; gene knockdown; human; human cell; human tissue; immunofluorescence; immunohistochemistry; MCF-7 cell line; MDA-MB-231 cell line; MDA-MB-468 cell line; metaplastic carcinoma; microarray analysis; priority journal; promoter region; reverse transcription polymerase chain reaction; SK-BR-3 cell line; spindle sarcomatous metaplasia; squamous cell metaplasia; T-47D cell line; upregulation; breast; breast tumor; cell transformation; epithelial mesenchymal transition; epithelium cell; female; gene expression regulation; genetics; metabolism; metaplasia; pathology; sarcoma; tumor cell line; Breast; Breast Neoplasms; Carcinosarcoma; Cell Line, Tumor; Cell Transformation, Neoplastic; Epithelial Cells; Epithelial-Mesenchymal Transition; Female; Fibrillin-1; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Humans; Immunohistochemistry; Metaplasia; Sarcoma; Transforming Growth Factor beta; Up-Regulation
Publisher
Elsevier B.V.
Type
journal article