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

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...

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Bibliographic Details
Published in:Breast cancer research and treatment 2012-02, Vol.132 (1), p.153-164
Main Authors: Yan, Xin-long, Fu, Chun-jiang, Chen, Lin, Qin, Jin-hua, Zeng, Quan, Yuan, Hong-feng, Nan, Xue, Chen, Hai-xu, Zhou, Jun-nian, Lin, Yan-li, Zhang, Xiao-mei, Yu, Cheng-ze, Yue, Wen, Pei, Xue-tao
Format: Article
Language:English
Subjects:
Animals
Antigens, Differentiation - metabolism
Biological and medical sciences
Breast cancer
Breast Neoplasms - pathology
Cancer research
Carcinoma, Ductal, Breast - pathology
Cell Differentiation
Cell Proliferation
Cell Shape
Cellular biology
Coculture Techniques
Epidermal growth factor
Epidermal Growth Factor - metabolism
Epidermal Growth Factor - physiology
Epidermal Growth Factor - secretion
Female
Gynecology. Andrology. Obstetrics
Humans
Mammary gland diseases
Medical sciences
Medicine
Medicine & Public Health
Mesenchymal Stromal Cells - metabolism
Mesenchymal Stromal Cells - secretion
Mice
Mice, Nude
Neoplasm Transplantation
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - secretion
Oncology
Phosphatidylinositol 3-Kinases - metabolism
Preclinical Study
Proto-Oncogene Proteins c-akt - metabolism
Receptor, Epidermal Growth Factor - metabolism
Signal Transduction
Spheroids, Cellular - metabolism
Spheroids, Cellular - secretion
Stem cells
Tissues
Tumor Burden
Tumor Cells, Cultured
Tumors
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Summary: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.
ISSN:0167-6806
1573-7217
DOI:10.1007/s10549-011-1577-0