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

Rokeya Akter, Kwangmin Kim, Hye Youn Kwon, Youngwan Kim, Young Woo Eom, Hye Mi Cho, Mee Yon Cho

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number3121
Issue number12
Publication statusPublished - 2022 Dec

Bibliographical note

Funding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) and funded by the Ministry of Education (2021R1F1A1046089).

Publisher Copyright:
© 2022 by the authors.

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)


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