Mesenchymal stem cells from primary breast cancer tissue promote cancer proliferation and enhance mammosphere formation partially via EGF/EGFR/Akt pathway

• DOI: 10.1007/s10549-011-1577-0
• Publication Date: 2011-05-16T08:48:04Z
• Authors: Xin-long Yan; Chun-jiang Fu; Lin Chen; Jin-hua Qin; Quan Zeng; Hong-feng Yuan; Xue Nan; Hai-xu Chen; Jun-nian Zhou; Yan-li Lin; Xiao-mei Zhang; Cheng-ze Yu; Wen Yue; Xue-tao Pei
• Keywords: 0303 health sciences; Epidermal Growth Factor; Carcinoma, Ductal, Breast; Mice, Nude; Breast Neoplasms; Cell Differentiation; Mesenchymal Stem Cells; Antigens, Differentiation; Coculture Techniques; 3. Good health; ErbB Receptors; Mice; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Neoplastic Stem Cells; Animals; Humans; Female; Cell Shape; Proto-Oncogene Proteins c-akt; Neoplasm Transplantation; Cell Proliferation; Signal Transduction

Mesenchymal stem cells (MSCs) play a critical role in promoting cancer progression. However, it is not clear whether MSCs are located in breast cancer tissues and correlated with tumor proliferation. The aim of this study was to investigate the presence of MSCs in breast cancer tissues and evaluate their interactions with cancer cells. We successfully isolated and identified MSCs from primary breast cancer tissues. Breast cancer-associated MSCs (BC-MSCs) showed homogenous immunophenotype, and possessed tri-lineage differentiation potential (osteoblast, adipocyte, and chondrocyte). When co-transplanted with cancer cells in a xenograft model in vivo, BC-MSCs significantly increased the volume and weight of tumors. We observed that BC-MSCs stimulated mammosphere formation in the transwell co-culture system in vitro. This effect was significantly suppressed by the EGF receptor inhibitor. We verified that BC-MSCs could secrete EGF and activate cancer cell's EGF receptors. Furthermore, our data showed that EGF derived from BC-MSCs could promote mammosphere formation via the PI3K/Akt signaling pathway. Our results confirmed the presence of MSC in primary breast cancer tissues, and they could provide a favorable microenvironment for tumor cell growth in vivo, partially enhance mammosphere formation via the EGF/EGFR/Akt pathway.