FHS seminar series by Prof. Xin-Yuan GUAN

Cancer associated fibroblasts (CAFs) play critical roles in the establishment of suitable tumor microenvironment. Using FGFR2 as a tracing marker, we systematically studied the process of mobilization, recruitment and maturation of CAFs in esophageal squamous cell carcinoma (ESCC) under the guidance of tumor cells. We found that FGFR2⁺ fibrocyte progenitors in bone marrow could be mobilized by cancer-secreted FGF2 and recruited into tumor sites via cancer-secreted CXCL12. Moreover, they differentiate into CAFs through the activation of YAP-TEAD complex which is trigger by directly contract with cancer cells. FGF2 and CXCR4 neutralizing antibodies could effectively block the mobilization and recruitment process of FGFR2⁺ CAFs. These findings give rise to new approaches that target CAFs before their incorporation into tumor stroma.