title: Estrogen-induced SDF-1α production promotes the progression of ER-negative breast cancer via the accumulation of MDSCs in the tumor microenvironment.
abstract: Estrogen plays a role in the processes of tumorigenesis, metastasis, and drug resistance in estrogen receptor (ER)-positive breast cancer (BC). Whether estrogen contributes to ER-negative BC is unclear. Here, we aimed to investigate whether estrogen could stimulate the secretion of stromal-derived factor-1 (SDF-1α) by cancer-associated fibroblasts (CAFs) to promote the progression of ER-negative BC. We transplanted ER-negative BC cells into ovariectomized mice, which was followed by continuous injection of estrogen, and found that estrogen promoted the tumorigenesis of BC. Furthermore, High levels of SDF-1α and tumor-infiltrating myeloid-derived suppressor cells (MDSCs) were detected in the estrogen treatment group. Estrogen stimulates secretion of SDF-1α by CAFs extracted from BC patients. Recombinant SDF-1α could recruit MDSCs isolated from bone marrow cells of mice. In addition, the co-culture of CAFs and MDSCs demonstrated that the recruitment of MDSCs was increased when CAFs were exposed to estrogen. Using AMD3100 to block the SDF-1α/CXCR4 axis or gemcitabine to delete MDSCs, we observed that both of these agents could neutralize the effect of estrogen on tumorigenesis. Together, these results suggest that estrogen may promote the progression of ER-negative BC by stimulating CAFs to secrete SDF-1α, which can recruit MDSCs to the tumor microenvironment to exert tumor-promoting effects.
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Liquan
authors.initials: L
authors.lastname: Ouyang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Weilong
authors.initials: W
authors.lastname: Chang
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Fang
authors.affiliation: Department of Clinical Medicine, Yichang Hospital of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Yichang 443000, Hubei, China.
authors.forename: Jieting
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science And Technology, Wuhan 430022, China.
authors.forename: Xincai
authors.initials: X
authors.lastname: Qu
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Fanjun
authors.initials: F
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000378:metabolism*; D002633:Chemotaxis; D018920:Coculture Techniques; D018450:Disease Progression; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D000072737:Myeloid-Derived Suppressor Cells / Q000166:cytology*; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D059016:Tumor Microenvironment
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004967:Estrogens; D011994:Recombinant Proteins