TY - JOUR T1 - Normal Mammary Fibroblasts Induce Reversion of the Malignant Phenotype in Human Primary Breast Cancer JF - Anticancer Research JO - Anticancer Res SP - 1525 LP - 1536 VL - 33 IS - 4 AU - ANNA-MARIA RÖMER AU - INKE LÜHR AU - ANDREAS KLEIN AU - ANDREAS FRIEDL AU - SUSANNE SEBENS AU - FRANK RÖSEL AU - NORBERT ARNOLD AU - ALEXANDER STRAUSS AU - WALTER JONAT AU - MARET BAUER Y1 - 2013/04/01 UR - http://ar.iiarjournals.org/content/33/4/1525.abstract N2 - Background/Aim: The tumor microenvironment plays a major role in tumor growth and progression. Its manipulation can lead to a reversion of the malignant phenotype. Here we explored the ability of normal mammary fibroblasts (HMFs) to induce reversion of the malignant phenotype of primary breast carcinoma cells (PBCs) in a three-dimensional (3D) context. Materials and Methods: PBCs were isolated from 13 primary breast carcinomas and cultured in 3D collagen-I gels as mono- or co-culture with HMFs. Results: In five co-cultures, PBCs exhibited reversion of their malignant phenotype, whereas PBCs in matched monocultures exhibited disorganized growth. Reversion, defined as the restoration of the complete baso-apical polarity axis, was confirmed with established polarity markers. Secretion of the tissue-specific glycoprotein MAM-6 into the acinar lumens and deposition of basement membrane indicated functional differentiation. Gene expression analysis revealed a set of differentially regulated genes which possibly affect the reversion process. These included MAL, ELF5, MAP6, ZMYND11 and SQLE. Conclusion: These findings highlight the significant role of fibroblasts in regulating the carcinoma phenotype. ER -