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 are also 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, scientists revealed that tumor-resident mesenchymal stem cells promote tumor growth through recruitment of macrophages.

Researchers led by Dr. SHI Yufang from the Institute of Health Sciences, Shanghai Institutes for Biological Sciences and Shanghai Jiao Tong University School of Medicine, in collaboration with scientists from Child Health Institute of New Jersey and Rutgers University, USA, have isolated tumor stromal MSCs (L-MSCs) from spontaneously developed lymphomas, characterized their tumor-promoting activity in tumor transplantation in animals, and studied their influence on immune responses of recipient animals in comparison to normal tissue MSCs (BM-MSCs). 

They found that unlike BM-MSCs, L-MSCs were more effective in recruiting monocytes/macrophages through overexpression of ligands for CCR2. These recruited macrophages promote tumor growth. Depletion of macrophages/monocytes or deficiency in CCR2 abrogated the tumor-promoting activity of L-MSCs. Importantly, TNF-alpha-pretreated BM-MSCs became similar to L-MSCs in 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-alpha" has been published online in Cell Stem Cell on November 15, 2012.

The study was funded by grants from the Ministry of Science and Technology of China, Scientific Innovation Project of the Chinese Academy of Science, National Natural Science Foundation of China, and the National Institutes of Health of the United States of America.

CONTACT:
SHI Yufang,
Key laboratory of Stem Cell Biology,
Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine,
Shanghai, China
Email: yufangshi@sibs.ac.cn
Tel: +86-21-63848329

Mechanism of Tumor-resident MSCs promote tumor growth.(Image by Dr. SHI Yufang 's Group)