PMID- 23564794 OWN - NLM STAT- MEDLINE DCOM- 20130611 LR - 20151119 IS - 1791-7530 (Electronic) IS - 0250-7005 (Linking) VI - 33 IP - 4 DP - 2013 Apr TI - Normal mammary fibroblasts induce reversion of the malignant phenotype in human primary breast cancer. PG - 1525-36 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. FAU - Romer, Anna-Maria AU - Romer AM AD - Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Kiel, Germany. FAU - Luhr, Inke AU - Luhr I FAU - Klein, Andreas AU - Klein A FAU - Friedl, Andreas AU - Friedl A FAU - Sebens, Susanne AU - Sebens S FAU - Rosel, Frank AU - Rosel F FAU - Arnold, Norbert AU - Arnold N FAU - Strauss, Alexander AU - Strauss A FAU - Jonat, Walter AU - Jonat W FAU - Bauer, Maret AU - Bauer M LA - eng PT - Journal Article PL - Greece TA - Anticancer Res JT - Anticancer research JID - 8102988 RN - 0 (Biomarkers, Tumor) SB - IM MH - Biomarkers, Tumor/*genetics MH - Breast/*cytology/metabolism MH - Breast Neoplasms/metabolism/*pathology MH - Cell Communication MH - Cell Culture Techniques MH - *Cell Transformation, Neoplastic MH - Coculture Techniques MH - Female MH - Fibroblasts/*cytology/metabolism MH - Gene Expression Profiling MH - Humans MH - Neoplasm Invasiveness MH - Oligonucleotide Array Sequence Analysis MH - Phenotype MH - Tumor Cells, Cultured MH - *Tumor Microenvironment EDAT- 2013/04/09 06:00 MHDA- 2013/06/12 06:00 CRDT- 2013/04/09 06:00 PHST- 2013/04/09 06:00 [entrez] PHST- 2013/04/09 06:00 [pubmed] PHST- 2013/06/12 06:00 [medline] AID - 33/4/1525 [pii] PST - ppublish SO - Anticancer Res. 2013 Apr;33(4):1525-36.