The tumor microenvironment has been suggested to participate in tumorigenesis, but the nature of the communication between cancer cells and the icroenvironment, especially in response to anticancer drugs, remains obscure. We determined that activation of the CCAAT/enhancer binding protein delta (CEBPD) response to Cisplatin and 5-Fluorouracil in cancer-associated macrophages and fibroblasts contributed to the metastasis, invasion, acquired chemoresistance and stemness of cancer cells. Specifically, CEBPD induction in macrophages and fibroblasts activates Pentraxin 3 (PTX3) expression. PTX3 promotes the expansion of breast cancer and that CEBPD and PTX3 expression in the stroma was associated with inferior disease-specific and metastasis-free survival in primary localized breast cancer. These finding suggest that PTX3 has a protumor activity and attributed to its protein inhibitors could function as promising drug for preventing cancer progression and the metastasis, invasion and progression of drug-resistant cancers.
