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

Ding,Jingxian; Guo,Chungen; Hu,Pinghua; Chen,Jun; Liu,Qiuming; Wu,Xiaobo; Cao,Yali; Wu,Jiong

doi:10.3892/ijo.2016.3680

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

Authors:
- Jingxian Ding
- Chungen Guo
- Pinghua Hu
- Jun Chen
- Qiuming Liu
- Xiaobo Wu
- Yali Cao
- Jiong Wu
View Affiliations

Affiliations: Department of Radiation Oncology, The Third Hospital of Nanchang, Nanchang, Jiangxi 330009, P.R. China, Department of Breast Surgery, The Third Hospital of Nanchang, Nanchang, Jiangxi 330009, P.R. China, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China
Published online on: September 6, 2016 https://doi.org/10.3892/ijo.2016.3680
Pages: 2064-2074

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

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.

View Figures

View References

1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI
2	Stanley ER, Berg KL, Einstein DB, Lee PS, Pixley FJ, Wang Y and Yeung YG: Biology and action of colony-stimulating factor-1. Mol Reprod Dev. 46:4–10. 1997. View Article : Google Scholar : PubMed/NCBI
3	Stanley ER, Berg KL, Einstein DB, Lee PS and Yeung YG: The biology and action of colony stimulating factor-1. Stem Cells. 12(Suppl 1): 15–24. 1994.PubMed/NCBI
4	Sapi E: The role of CSF-1 in normal physiology of mammary gland and breast cancer: An update. Exp Biol Med (Maywood). 229:1–11. 2004.
5	Chambers AF, Groom AC and MacDonald IC: Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer. 2:563–572. 2002. View Article : Google Scholar : PubMed/NCBI
6	Hughes R, Qian BZ, Rowan C, Muthana M, Keklikoglou I, Olson OC, Tazzyman S, Danson S, Addison C, Clemons M, et al: Perivascular M2 macrophages stimulate tumor relapse after chemotherapy. Cancer Res. 75:3479–3491. 2015. View Article : Google Scholar : PubMed/NCBI
7	Sugimura K, Miyata H, Tanaka K, Takahashi T, Kurokawa Y, Yamasaki M, Nakajima K, Takiguchi S, Mori M and Doki Y: High infiltration of tumor-associated macrophages is associated with a poor response to chemotherapy and poor prognosis of patients undergoing neoadjuvant chemotherapy for esophageal cancer. J Surg Oncol. 111:752–759. 2015. View Article : Google Scholar : PubMed/NCBI
8	Sasayama T, Tanaka K, Mizowaki T, Nagashima H, Nakamizo S, Tanaka H, Nishihara M, Mizukawa K, Hirose T, Itoh T, et al: Tumor-associated macrophages associate with cerebrospinal fluid interleukin-10 and survival in primary central nervous system lymphoma (PCNSL). Brain Pathol. 26:479–487. 2016. View Article : Google Scholar
9	Gordon S: Alternative activation of macrophages. Nat Rev Immunol. 3:23–35. 2003. View Article : Google Scholar : PubMed/NCBI
10	Svensson J, Jenmalm MC, Matussek A, Geffers R, Berg G and Ernerudh J: Macrophages at the fetal-maternal interface express markers of alternative activation and are induced by M-CSF and IL-10. J Immunol. 187:3671–3682. 2011. View Article : Google Scholar : PubMed/NCBI
11	Wynn TA, Chawla A and Pollard JW: Macrophage biology in development, homeostasis and disease. Nature. 496:445–455. 2013. View Article : Google Scholar : PubMed/NCBI
12	Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M and Ley K: Development of monocytes, macrophages, and dendritic cells. Science. 327:656–661. 2010. View Article : Google Scholar : PubMed/NCBI
13	Park KY, Li G and Platt MO: Monocyte-derived macrophage assisted breast cancer cell invasion as a personalized, predictive metric to score metastatic risk. Sci Rep. 5:138552015. View Article : Google Scholar : PubMed/NCBI
14	Yu KD, Li JJ, Di GH, Wu J, Shen ZZ and Shao ZM: A straight-forward but not piecewise relationship between age and lymph node status in Chinese breast cancer patients. PLoS One. 5:e110352010. View Article : Google Scholar
15	Hannan NJ, Bambang K, Kaitu'u-Lino TJ, Konje JC and Tong S: A bioplex analysis of cytokines and chemokines in first trimester maternal plasma to screen for predictors of miscarriage. PLoS One. 9:e933202014. View Article : Google Scholar : PubMed/NCBI
16	Lee KS, Chung JH, Lee KH, Shin MJ, Oh BH and Hong CH: Bioplex analysis of plasma cytokines in Alzheimer's disease and mild cognitive impairment. Immunol Lett. 121:105–109. 2008. View Article : Google Scholar : PubMed/NCBI
17	Kim YW, Kim SK, Kim CS, Kim IY, Cho MY and Kim NK: Association of serum and intratumoral cytokine profiles with tumor stage and neutrophil lymphocyte ratio in colorectal cancer. Anticancer Res. 34:3481–3487. 2014.PubMed/NCBI
18	Shigeoka M, Urakawa N, Nakamura T, Nishio M, Watajima T, Kuroda D, Komori T, Kakeji Y, Semba S and Yokozaki H: Tumor associated macrophage expressing CD204 is associated with tumor aggressiveness of esophageal squamous cell carcinoma. Cancer Sci. 104:1112–1119. 2013. View Article : Google Scholar : PubMed/NCBI
19	Kaku Y, Imaoka H, Morimatsu Y, Komohara Y, Ohnishi K, Oda H, Takenaka S, Matsuoka M, Kawayama T, Takeya M, et al: Overexpression of CD163, CD204 and CD206 on alveolar macrophages in the lungs of patients with severe chronic obstructive pulmonary disease. PLoS One. 9:e874002014. View Article : Google Scholar : PubMed/NCBI
20	Györffy B, Lanczky A, Eklund AC, Denkert C, Budczies J, Li Q and Szallasi Z: An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1,809 patients. Breast Cancer Res Treat. 123:725–731. 2010. View Article : Google Scholar
21	Hass R, Bartels H, Topley N, Hadam M, Köhler L, Goppelt-Strübe M and Resch K: TPA-induced differentiation and adhesion of U937 cells: Changes in ultrastructure, cytoskeletal organization and expression of cell surface antigens. Eur J Cell Biol. 48:282–293. 1989.PubMed/NCBI
22	Fulton RJ, McDade RL, Smith PL, Kienker LJ and Kettman JR Jr: Advanced multiplexed analysis with the FlowMetrix system. Clin Chem. 43:1749–1756. 1997.PubMed/NCBI
23	Schmieder A, Michel J, Schönhaar K, Goerdt S and Schledzewski K: Differentiation and gene expression profile of tumor-associated macrophages. Semin Cancer Biol. 22:289–297. 2012. View Article : Google Scholar : PubMed/NCBI
24	Obeid E, Nanda R, Fu YX and Olopade OI: The role of tumor-associated macrophages in breast cancer progression (Review). Int J Oncol. 43:5–12. 2013.PubMed/NCBI
25	Kennedy BC, Showers CR, Anderson DE, Anderson L, Canoll P, Bruce JN and Anderson RC: Tumor-associated macrophages in glioma: Friend or foe? J Oncol. 2013:4869122013. View Article : Google Scholar : PubMed/NCBI
26	Marino N, Woditschka S, Reed LT, Nakayama J, Mayer M, Wetzel M and Steeg PS: Breast cancer metastasis: Issues for the personalization of its prevention and treatment. Am J Pathol. 183:1084–1095. 2013. View Article : Google Scholar : PubMed/NCBI
27	Quail DF and Joyce JA: Microenvironmental regulation of tumor progression and metastasis. Nat Med. 19:1423–1437. 2013. View Article : Google Scholar : PubMed/NCBI
28	Hanahan D and Coussens LM: Accessories to the crime: Functions of cells recruited to the tumor microenvironment. Cancer Cell. 21:309–322. 2012. View Article : Google Scholar : PubMed/NCBI
29	Kelly PM, Davison RS, Bliss E and McGee JO: Macrophages in human breast disease: A quantitative immunohistochemical study. Br J Cancer. 57:174–177. 1988. View Article : Google Scholar : PubMed/NCBI
30	Medrek C, Pontén F, Jirström K and Leandersson K: The presence of tumor associated macrophages in tumor stroma as a prognostic marker for breast cancer patients. BMC Cancer. 12:3062012. View Article : Google Scholar : PubMed/NCBI
31	Tsutsui S, Yasuda K, Suzuki K, Tahara K, Higashi H and Era S: Macrophage infiltration and its prognostic implications in breast cancer: The relationship with VEGF expression and microvessel density. Oncol Rep. 14:425–431. 2005.PubMed/NCBI
32	Chaturvedi P, Gilkes DM, Takano N and Semenza GL: Hypoxia-inducible factor-dependent signaling between triple-negative breast cancer cells and mesenchymal stem cells promotes macrophage recruitment. Proc Natl Acad Sci USA. 111:E2120–E2129. 2014. View Article : Google Scholar : PubMed/NCBI
33	Lin EY, Nguyen AV, Russell RG and Pollard JW: Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med. 193:727–740. 2001. View Article : Google Scholar : PubMed/NCBI
34	Wyckoff J, Wang W, Lin EY, Wang Y, Pixley F, Stanley ER, Graf T, Pollard JW, Segall J and Condeelis J: A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res. 64:7022–7029. 2004. View Article : Google Scholar : PubMed/NCBI
35	Pollard JW: Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer. 4:71–78. 2004. View Article : Google Scholar : PubMed/NCBI
36	Qian BZ, Li J, Zhang H, Kitamura T, Zhang J, Campion LR, Kaiser EA, Snyder LA and Pollard JW: CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature. 475:222–225. 2011. View Article : Google Scholar : PubMed/NCBI
37	Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, Baehner FL, Walker MG, Watson D, Park T, et al: A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 351:2817–2826. 2004. View Article : Google Scholar : PubMed/NCBI
38	Shabo I, Stål O, Olsson H, Doré S and Svanvik J: Breast cancer expression of CD163, a macrophage scavenger receptor, is related to early distant recurrence and reduced patient survival. Int J Cancer. 123:780–786. 2008. View Article : Google Scholar : PubMed/NCBI
39	Lin JA, Lin FY and Chen TL: Bone components downregulate expression of toll-like receptor 4 on the surface of human monocytic U937 cells: A cell model for postfracture immune dysfunction. Mediators Inflamm. 2015:8965762015. View Article : Google Scholar : PubMed/NCBI
40	Martin-Manso G, Galli S, Ridnour LA, Tsokos M, Wink DA and Roberts DD: Thrombospondin 1 promotes tumor macrophage recruitment and enhances tumor cell cytotoxicity of differentiated U937 cells. Cancer Res. 68:7090–7099. 2008. View Article : Google Scholar : PubMed/NCBI
41	Yang XV, Banerjee Y, Fernández JA, Deguchi H, Xu X, Mosnier LO, Urbanus RT, de Groot PG, White-Adams TC, McCarty OJ, et al: Activated protein C ligation of ApoER2 (LRP8) causes Dab1-dependent signaling in U937 cells. Proc Natl Acad Sci USA. 106:274–279. 2009. View Article : Google Scholar : PubMed/NCBI