RT Journal Article
SR Electronic
T1 Normal Mammary Fibroblasts Induce Reversion of the Malignant Phenotype in Human Primary Breast Cancer
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 1525
OP 1536
VO 33
IS 4
A1 ANNA-MARIA RÖMER
A1 INKE LÜHR
A1 ANDREAS KLEIN
A1 ANDREAS FRIEDL
A1 SUSANNE SEBENS
A1 FRANK RÖSEL
A1 NORBERT ARNOLD
A1 ALEXANDER STRAUSS
A1 WALTER JONAT
A1 MARET BAUER
YR 2013
UL http://ar.iiarjournals.org/content/33/4/1525.abstract
AB 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.