RUNX1 promotes angiogenesis in colorectal cancer by regulating the crosstalk between tumor cells and tumor associated macrophages

Xuxue Guo; Haonan Zhang; Chengcheng He; Kaiwen Qin; Qiuhua Lai; Yuxin Fang; Qianhui Chen; Weize Li; Yiqing Wang; Xinke Wang; Aimin Li; Side Liu; Qingyuan Li

doi:10.1186/s40364-024-00573-1

RUNX1 promotes angiogenesis in colorectal cancer by regulating the crosstalk between tumor cells and tumor associated macrophages

Biomark Res. 2024 Feb 28;12(1):29. doi: 10.1186/s40364-024-00573-1.

Authors

Xuxue Guo^#^{1

2}, Haonan Zhang^#^{1

3}, Chengcheng He^{1

3}, Kaiwen Qin^{1

4}, Qiuhua Lai¹, Yuxin Fang¹, Qianhui Chen⁵, Weize Li⁴, Yiqing Wang^{6

7}, Xinke Wang¹, Aimin Li¹, Side Liu^{8

9}, Qingyuan Li¹⁰

Affiliations

¹ Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou Avenue North, Guangzhou, 510515, People's Republic of China.
² Department of Gastroenterology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
³ Department of Gastroenterology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
⁴ The First School of Clinical Medicine), Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
⁵ State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Hepatology Unit and Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
⁶ Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
⁷ Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
⁸ Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou Avenue North, Guangzhou, 510515, People's Republic of China. sideliu@smu.edu.cn.
⁹ Pazhou Lab, Guangzhou, Guangdong, China. sideliu@smu.edu.cn.
¹⁰ Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou Avenue North, Guangzhou, 510515, People's Republic of China. liqingyuan09@smu.edu.cn.

^# Contributed equally.

Abstract

Colorectal cancer (CRC) is a common malignancy worldwide. Angiogenesis and metastasis are the critical hallmarks of malignant tumor. Runt-related transcription factor 1 (RUNX1), an efficient transcription factor, facilitates CRC proliferation, metastasis and chemotherapy resistance. We aimed to investigate the RUNX1 mediated crosstalk between tumor cells and M2 polarized tumor associated macrophages (TAMs) in CRC, as well as its relationship with neoplastic angiogenesis. We found that RUNX1 recruited macrophages and induced M2 polarized TAMs in CRC by promoting the production of chemokine 2 (CCL2) and the activation of Hedgehog pathway. In addition, we found that the M2 macrophage-specific generated cytokine, platelet-derived growth factor (PDGF)-BB, promoted vessel formation both in vitro and vivo. PDGF-BB was also found to enhance the expression of RUNX1 in CRC cell lines, and promote its migration and invasion in vitro. A positive feedback loop of RUNX1 and PDGF-BB was thus formed. In conclusion, our data suggest that RUNX1 promotes CRC angiogenesis by regulating M2 macrophages during the complex crosstalk between tumor cells and TAMs. This observation provides a potential combined therapy strategy targeting RUNX1 and TAMs-related PDGF-BB in CRC.

Keywords: Angiogenesis; Colorectal cancer; M2 polarization; RUNX1; Tumor associated macrophages.