CSF1 is involved in breast cancer progression through inducing monocyte differentiation and homing.
Despite the great progress in breast cancer research and treatment, measures for efficient targeting of triple‑negative breast cancer (TNBC) are still lacking. The well‑established dependency of cancer cells on their microenvironment suggests that targeting the tumor niche might form a novel therapeutic approach. We identified the tumor‑associated macrophage (TAM) infiltration in breast cancer tissues by immunohistochemistry, and analyzed overall survival (OS). U937 co‑cultures with MDA‑MB‑231, MDA‑MB‑468 and MCF‑7, respectively, to simulate in vivo cellular interactions were assessed. In hormone‑independent breast cancer cell conditioned media (CM), U937 differentiates into M2 macrophage as identified by morphological changes and expression of specific surface antigens CD163 and CD204. Moreover, MDA‑MB‑231 recruits U937, and colony‑stimulating factor 1 (CSF1) level in MDA‑MB‑231 and MDA‑MB‑468 CM is much higher than that of MCF‑7. Overexpression of CSF1 in MCF‑7 fails to rebuild its aggressiveness both in vitro and in vivo since CSF1 was not found extracellularly, while genetic inhibition of CSF1 in MDA‑MB‑231 abrogates TAM infiltration and consequently reduces tumorigenesis in non‑obese diabetic/severe combined immunodeficient (NOD/SCID) mice. Using various strategies we demonstrate that CSF1‑induced TAMs specifically support breast cancer progression. Importantly, our results may reveal the efficacy of using targeted therapy against tumor niche and indicate that CSF1 inhibition may limit some breast cancer progression.
Department of Radiation Oncology, The Third Hospital of Nanchang, Nanchang, Jiangxi 330009, P.R. China.
Jingxian
J
Ding
Department of Breast Surgery, The Third Hospital of Nanchang, Nanchang, Jiangxi 330009, P.R. China.
Chungen
C
Guo
Department of Breast Surgery, The Third Hospital of Nanchang, Nanchang, Jiangxi 330009, P.R. China.
Pinghua
P
Hu
Department of Breast Surgery, The Third Hospital of Nanchang, Nanchang, Jiangxi 330009, P.R. China.
Jun
J
Chen
Department of Breast Surgery, The Third Hospital of Nanchang, Nanchang, Jiangxi 330009, P.R. China.
Qiuming
Q
Liu
Department of Breast Surgery, The Third Hospital of Nanchang, Nanchang, Jiangxi 330009, P.R. China.
Xiaobo
X
Wu
Department of Breast Surgery, The Third Hospital of Nanchang, Nanchang, Jiangxi 330009, P.R. China.
Yali
Y
Cao
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
Jiong
J
Wu
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D018450:Disease Progression; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009000:Monocytes / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
D016173:Macrophage Colony-Stimulating Factor