EMR1/ADGRE1 Expression in Cancer Cells Upregulated by Tumor-Associated Macrophages Is Related to Poor Prognosis in Colorectal Cancer

• Published in: Biomedicines Vol. 10; no. 12; p. 3121
• Main Authors: Akter, Rokeya, Kim, Kwangmin, Kwon, Hye Youn, Kim, Youngwan, Eom, Young Woo, Cho, Hye-Mi, Cho, Mee-Yon
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.12.2022; MDPI
• Subjects: adhesion G protein-coupled receptor EMR1/ADGRE1; Cancer cells; Cancer therapies; CD163 antigen; CD86 antigen; Cell culture; Clinical significance; Colon cancer; Colorectal cancer; Colorectal carcinoma; Cytokines; Epidermal growth factor; Gene expression; Genetic aspects; Health aspects; Interleukin 6; lymph node metastasis; Lymph nodes; macrophage activation; Macrophages; Medical prognosis; Metastases; Metastasis; Myeloid cells; Nitric-oxide synthase; Polarization; Prognosis; Reagents; recurrence-free survival; Risk factors; Stains & staining; Tumor cells; tumor-associated macrophages; South Korea; Minneapolis Minnesota; United Kingdom > UK; United States > US; colorectal cancer; macrophage activation; adhesion G protein-coupled receptor EMR1/ADGRE1; recurrence-free survival; lymph node metastasis; tumor-associated macrophages
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines10123121

EMR1, a member of the adhesion G protein-coupled receptor family (ADGRE1), is a macrophage marker that is abnormally expressed in cancer cells. However, its clinical significance in colorectal cancer (CRC) is not well-known. In this investigation, EMR1 expression in tumor cells (EMR1-TC) was found in 91 (22.8%) of the 399 CRC samples tested by immunohistochemical staining and showed a significant relationship with lymph node metastasis. Furthermore, EMR1-TC was significantly associated with CD68 CD163 tumor-associated macrophages (TAMs), and CRC with a high combined EMR1-TC CD68 CD163 score showed worse recurrence-free survival prognosis. In an in vitro co-culture assay of colon cancer cells with myeloid cells, we found that EMR1 expression significantly upregulated in cancer cells was induced by macrophages. In addition, there was increased expression of M2 markers (CD163 and interleukin-6 & 10) in myeloid portion, while that of M1 markers (CD86 and iNOS) remained unchanged. Accordingly, upon treatment with M2 macrophage polarization inhibitors (O-ATP, trametinib, bardoxolone methyl), EMR1 expression reduced significantly, along with M2 markers (CD163 and interleukin-6 & 10). In conclusion, EMR1-TC was a high-risk factor for lymph node metastasis and correlated with poor recurrence free survival, particularly in patients with TAM-rich CRC. Furthermore, EMR1 expression in colon cancer cells may be related to M2 macrophage polarization and vice versa.