Biological Characteristics and Genetic Heterogeneity between Carcinoma-Associated Fibroblasts and Their Paired Normal Fibroblasts in Human Breast Cancer

作者：Qiongle Peng, Liuyang Zhao, Yixuan Hou, Yan Sun, Liyang Wang, Haojun Luo, Huimin Peng, Manran Liu · 发表于：PLoS ONE · 年份：2013 · DOI：10.1371/journal.pone.0060321 · 被引用次数：91 · 研究领域：Cancer Cells and Metastasis、Cell Adhesion Molecules Research、Bone and Dental Protein Studies

BACKGROUND: The extensional signals in cross-talk between stromal cells and tumor cells generated from extracellular matrix molecules, soluble factor, and cell-cell adhesion complexes cooperate at the extra- and intracellular level in the tumor microenvironment. CAFs are the primary type of stromal cells in the tumor microenvironment and play a pivotal role in tumorigenesis and development. Hitherto, there is hardly any systematic analysis of the intrinsic relationship between CAFs function and its abnormal signaling pathway. The extreme complexity of CAFs' features and their role in tumor development are needed to be further investigated. METHODOLOGY/PRINCIPAL FINDINGS: We primary cultured CAFs and NFs from early stages of breast cancer tissue and identified them using their biomarker by immunohistochemistry for Fibronectin, α-SMA and FAP. Microarray was applied to analyze gene expression profiles of human breast CAFs and the paired NFs. The Up-regulated genes classified by Gene Ontology, signal pathways enriched by DAVID pathway analysis. Abnormal signaling pathways in breast cancer CAFs are involved in cell cycle, cell adhesion, signal transduction and protein transport being reported in CAFs derived from other tumors. Significantly, the altered ATM signaling pathway, a set of cell cycle regulated signaling, and immune associated signaling are identified to be changed in CAFs. CONCLUSIONS/SIGNIFICANCE: CAFs have the vigorous ability of proliferation and potential of invasi...