Mesenchymal stem/stromal cells (MSCs) actively migrate to the tumour sites and construct the tumour microenvironment. Within tumor, they acquire the ability to regulate tumor progression through secreting growth factors and chemokines, enhancing capillary formation and modulating anti-tumour immune responses.
A team led by Dr. SHI Yufang at Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences has reported in Cell Stem Cell (2012) that this tumor promotion capability is only possessed by tumour-associated MSCs, but not bone marrow MSCs. Detailed analysis found that these tumour-associated MSCs could secrete higher levels of CCR2 ligands (CCL-2, CCL-7, CCL-12), which recruit monocytes and macrophages to tumours. Additionally, tumour-associated MSCs could also endow the newly arrived bone marrow-MSCs with the ability to produce more CCR2 ligands and further promote tumour growth. However, the formation of these tumour-associated MSCs remains largely unknown.
Recently, graduate students DU Liming, LIN Liangyu and Dr. WANG Ying at Dr. SHI Yufang’s team conducted a series of research on the ménage-à-trois among tumour cells, MSCs and immune cells during the tumour growth. In this work, they found that exosomes secreted by tumour cells take the action on MSCs. By uptake of exosomes, MSCs gained the ability to promote tumour growth.
Compared with normal MSCs, tumour cell-derived exosomes educated MSCs (TE-MSCs) could recruit more monocytes and macrophages into tumours and build the tumour-favorable microenvironment. Depletion of macrophages or blockade of their infiltration in the tumours abolished the tumour promotion by TE-MSCs.
This study proved that exosomes secreted by tumour cells can educate newly arrived naïve MSCs at the tumor site and help them to change into tumour-associated MSCs. It provides new insights into the understanding of the interplay among tumour cells, MSCs and immune cells during tumour growth.
This study entitled “Tumour cell-derived exosomes endow mesenchymal stromal cells with tumour-promotion capabilities” has been published in Oncogene on May 2, 2016.
This work was supported by the Ministry of Science and Technology of China, National Natural Science Foundation of China, Science and Technology Commission of Shanghai Municipality and Chinese Academy of Sciences.
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