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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Biomarkers, Tumor, Breast, Breast Neoplasms, Cell Communication, Cell Culture Techniques, Cell Transformation, Neoplastic, Coculture Techniques, Female, Fibroblasts, Gene Expression Profiling, Humans, Neoplasm Invasiveness, Oligonucleotide Array Sequence Analysis, Phenotype, Tumor Cells, Cultured, Tumor Microenvironment.
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Do normal mammary fibroblasts induce reversion of the malignant phenotype in human primary breast cancer? Context: 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. PBCs were isolated from 13 primary breast carcinomas and cultured in 3D collagen-I gels as mono- or co-culture with HMFs. 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.
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These findings highlight the significant role of fibroblasts in regulating the carcinoma phenotype. Final Decision: yes