Mesenchymal stromal cells (MSCs) widely exist in almost all tissues. When tumour occurs, MSCs actively infiltrate into tumours and become a key component of the tumour microenvironment.

Previous study conducted by Dr. SHI Yufang’s lab demonstrated that tumour derived MSCs promoted tumour growth by recruiting monocytes and macrophages into the tumour. This process is mediated by the high amounts of C-C chemokine receptor type 2 (CCR2) ligands secreted by tumour MSCs. Similar pro-tumour effect can be achieved by tumour necrosis factora (TNFα)-stimulated MSCs. However, the function of MSCs in tumour metastasis remains elusive.

The research team led by Drs. WANG Ying at the Institute of Health Sciences, Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences and SHI Yufang at School of Medicine of Shanghai Jiao Tong University revealed that TNFα-activated MSCs strikingly enhanced breast cancer metastasis. Analysis of the chemokine profiles of TNFα-activated MSCs and normal MSCs discovered that TNFα-activated MSCs exhibited much higher expression of CCL5, CCR2 and CXCR2 ligands.

Genetical and pharmacological block of these chemokine expression or function verified that CXCR2 ligands (CXCL1, CXCL2 and CXCL5) were essential in mediating the pro-metastasis effect of TNFα-activated MSCs by efficiently recruiting CXCR2⁺ neutrophils into tumours. After interaction with CXCR2⁺ neutrophils, tumour cells exhibited dramatically elevated metastasis-related genes, including CXCR4, CXCR7, MMP12, MMP13, IL-6, and TGFb.

In IL-8 (another ligand of CXCR2)^high human breast cancer samples, researchers also observed similar alterations of gene expression.

This study provides new insights into understanding the crosstalk among immune cells, MSCs, and tumour cells during tumour metastasis.

The study was published in Oncogene, reporting the function and regulatory networks between mesenchymal stromal cells and neutrophils in tumour metastasis.

This work was mainly supported by the Ministry of Science and Technology of China, National Natural Science Foundation of China and Chinese Academy of Sciences.