CSF1 is involved in breast cancer progression through inducing monocyte differentiation and homing

Abstract

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.

Neuropilin1 Expression Acts as a Prognostic Marker in Stomach Adenocarcinoma by Predicting the Infiltration of Treg Cells and M2 Macrophages

“…Activated Treg cells also evade tumor immunity by inhibiting effector cells, such as CD4 + and CD8 + T cells [72]. In addition, tumor infiltrated M2 macrophages exhibit a tumorigenic effect by producing high levels of IL-10 and TGF-β1 [73]. NRP1 enhances Treg cells for tumor infiltration and promotes macrophage differentiation, as preparation for the activation of immune evasion responses [60,74].…”

“…CSF1, which regulates the macrophage lineage, has been found to increase the expression of macrophages and TAM, control the differentiation and function of M2 macrophages, and act as an angiogenesis switch [71,75,76]. According to a related study, the gene inhibition of CSF1 in breast cancer cells affects tumor formation in immunodeficient mice [73]. In addition, multiple tumor cell injections in the mouse liver metastasis models were found to increase the number of CD4+ CD25 + Treg cells and the expression of cytokines IL-10 and TGFβ-1 [77].…”

Differential Impact of Calcitriol and Its Analogs on Tumor Stroma in Young and Aged Ovariectomized Mice Bearing 4T1 Mammary Gland Cancer

“…Furthermore, macrophage colony-stimulating factor (M-CSF, encoded by Csf1) is an essential factor for the maturation of monocytes/macrophages. Ding et al demonstrated that the more aggressive human MDA-MB-231 and MDA-MB-468 breast cancer cell lines show a higher expression of M-CSF than MCF-7 cells with less invasive phenotype [52]. Moreover, it has been noted that the enhanced expression of Csf1 was correlated with a worse prognosis of overall survival in breast cancer [53] and with increased infiltration of TAMs in colorectal cancer [54].…”

Identification of an Unfavorable Immune Signature in Advanced Lung Tumors from Nrf2-Deficient Mice

“…Colony sti-mulating factor 1 (Csf1) is involved in cancer growth, survival, and metastasis. Blockade of CSF1/CSF1R reprograms TAMs to enhance antigen presentation, thus improving the therapeutic effects of immunotherapies (1,19,30,89).…”