International Cooperation

MSCs Promote Tumor Growth through Recruiting Macrophages

Mesenchymal stem cells (MSCs) exist in almost all types of tissues and are believed to play a central role in tissue regeneration, wound repair, and maintenance of tissue homeostasis. In recent years, MSCs are also identified as one of the major components of the tumor stroma, and believed to be the precursors of tumor-associated fibroblasts. However, the tumor promotion function of MSCs residing in tumors and their distinctions from MSCs in normal tissues are largely unknown. Recently, researchers led by Dr. Shi Yufang from the Institute of Health Sciences, Shanghai Institutes for Biological Sciences, CAS and the Shanghai Jiao Tong University School of Medicine revealed tumor resident MSCs promote tumor growth through recruiting macrophages. This work was a result of collaboration with scientists from the Child Health Institute of New Jersey and Rutgers University. In the last few years, Dr. Shi’s group investigated the molecular mechanisms underlining the interaction between MSCs and immune responses, published several key papers and made significant contribution to this field. In the current study, they isolated tumor stromal MSCs (L-MSCs) from spontaneously developed lymphomas, characterized their tumor-promoting activity in tumor transplantation animal models, and studied their influence on immune responses of recipient animals in comparison to normal tissue MSCs (BM-MSCs). Dr. Shi’s group found that unlike BM-MSCs, L-MSCs were more effective in recruiting monocytes/macrophages through overexpression of ligands for CCR2: CCL2, CCL7, and CCL12. These recruited macrophages promote tumor growth. Depletion of macrophages/monocytes or deficiency in CCR2 abrogated the tumor-promoting activity of L-MSCs. Importantly, TNF-α-pretreatment coverts BM-MSCs into L-MSCs as indicated by their chemokine production profile and ability to promote tumorigenesis of lymphoma, melanoma, and breast carcinoma. The studies provide important insights into the role of MSCs in guiding the formation of the tumor microenvironment, as well as the importance of inflammation in endorsing this effect. Strategies that target MSC-monocyte/macrophage crosstalk should provide novel strategies for cancer therapy. The study entitled "CCR2-Dependent Recruitment of Macrophages by Tumor-Educated Mesenchymal Stromal Cells Promotes Tumor Development and is Mimicked by TNF-α" was published online in Cell Stem Cell on Nov. 15th, 2012.