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The myeloid cell biomarker EMR1 is ectopically expressed in colon cancer

Ali, Haytham ; Olsson, Lina ; Lindmark, Gudrun LU ; Hammarström, Marie Louise ; Hammarström, Sten and Sitohy, Basel (2021) In Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 43(1). p.209-223
Abstract

OBJECTIVE: The microenvironment of colon cancer (CC) is heterogeneous including cells of myeloid lineage affecting tumor growth and metastasis. Two functional subtypes of myeloid cells have been identified; one (M1) is tumor-inhibitory and the other one (M2) is tumor-promoting. Whether the three myeloid markers EMR1, CD206 and CD86 are expressed only in the infiltrating myeloid cells or also in the tumor cells was investigated. METHODS: Expression of the myeloid markers was investigated in CC at the mRNA and protein levels in primary tumors and lymph nodes. mRNA expression was also determined in 5 CC cell lines. Protein expression was investigated by two-color immunofluorescence and consecutive-sections-immune-staining combined with... (More)

OBJECTIVE: The microenvironment of colon cancer (CC) is heterogeneous including cells of myeloid lineage affecting tumor growth and metastasis. Two functional subtypes of myeloid cells have been identified; one (M1) is tumor-inhibitory and the other one (M2) is tumor-promoting. Whether the three myeloid markers EMR1, CD206 and CD86 are expressed only in the infiltrating myeloid cells or also in the tumor cells was investigated. METHODS: Expression of the myeloid markers was investigated in CC at the mRNA and protein levels in primary tumors and lymph nodes. mRNA expression was also determined in 5 CC cell lines. Protein expression was investigated by two-color immunofluorescence and consecutive-sections-immune-staining combined with morphometry using specific antibodies for the myeloid cell markers and the epithelial cell markers CEACAM5 and EpCAM. RESULTS: EMR1 and CD86, but not CD206, mRNA levels were significantly higher in CC primary tumors compared to apparently normal colon tissue (P <  0.0001). EMR1 mRNA levels were significantly higher in both hematoxylin-eosin positive (H&E(+)) and H&E(-) lymph nodes of CC patients compared to control nodes (P = 0.03 and P = 0.01, respectively). EMR1 and CD206 mRNAs were expressed in 4/5 and 5/5 CC cell lines, respectively, while CD86 mRNA was not expressed. Immuno-morphometry revealed that about 20% of the tumor cells expressed EMR1 and CD206. Positive cells were tumor cells as revealed by anti-CEACAM5 and anti-EpCAM staining. The number of EMR1, CD206 and CD86 positive cells were significantly increased in CC primary tumors compared to normal colon tissue (P <  0.0001). However, CD206 was also expressed in normal colonocytes. Only EMR1 showed significantly increased numbers of positive tumor cells in H&E(+) nodes compared to H&E(-) nodes (P = 0.001). EMR1 expression in CC tumor cells correlated with CXCL17 expressing tumor cells. CONCLUSION: EMR1, like the chemokine CXCL17, is ectopically expressed in colon cancer possibly in the same cancer cells.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
CD206, CD86, chemokines, EMR1, epithelial cell markers
in
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine
volume
43
issue
1
pages
15 pages
publisher
Springer
external identifiers
  • scopus:85115819829
  • pmid:34486997
ISSN
1423-0380
DOI
10.3233/TUB-200082
language
English
LU publication?
yes
id
8b5a3dd4-218d-41e9-a6ed-862c669c98b0
date added to LUP
2021-10-20 10:47:20
date last changed
2024-06-16 21:10:18
@article{8b5a3dd4-218d-41e9-a6ed-862c669c98b0,
  abstract     = {{<p>OBJECTIVE: The microenvironment of colon cancer (CC) is heterogeneous including cells of myeloid lineage affecting tumor growth and metastasis. Two functional subtypes of myeloid cells have been identified; one (M1) is tumor-inhibitory and the other one (M2) is tumor-promoting. Whether the three myeloid markers EMR1, CD206 and CD86 are expressed only in the infiltrating myeloid cells or also in the tumor cells was investigated. METHODS: Expression of the myeloid markers was investigated in CC at the mRNA and protein levels in primary tumors and lymph nodes. mRNA expression was also determined in 5 CC cell lines. Protein expression was investigated by two-color immunofluorescence and consecutive-sections-immune-staining combined with morphometry using specific antibodies for the myeloid cell markers and the epithelial cell markers CEACAM5 and EpCAM. RESULTS: EMR1 and CD86, but not CD206, mRNA levels were significantly higher in CC primary tumors compared to apparently normal colon tissue (P &lt;  0.0001). EMR1 mRNA levels were significantly higher in both hematoxylin-eosin positive (H&amp;E(+)) and H&amp;E(-) lymph nodes of CC patients compared to control nodes (P = 0.03 and P = 0.01, respectively). EMR1 and CD206 mRNAs were expressed in 4/5 and 5/5 CC cell lines, respectively, while CD86 mRNA was not expressed. Immuno-morphometry revealed that about 20% of the tumor cells expressed EMR1 and CD206. Positive cells were tumor cells as revealed by anti-CEACAM5 and anti-EpCAM staining. The number of EMR1, CD206 and CD86 positive cells were significantly increased in CC primary tumors compared to normal colon tissue (P &lt;  0.0001). However, CD206 was also expressed in normal colonocytes. Only EMR1 showed significantly increased numbers of positive tumor cells in H&amp;E(+) nodes compared to H&amp;E(-) nodes (P = 0.001). EMR1 expression in CC tumor cells correlated with CXCL17 expressing tumor cells. CONCLUSION: EMR1, like the chemokine CXCL17, is ectopically expressed in colon cancer possibly in the same cancer cells.</p>}},
  author       = {{Ali, Haytham and Olsson, Lina and Lindmark, Gudrun and Hammarström, Marie Louise and Hammarström, Sten and Sitohy, Basel}},
  issn         = {{1423-0380}},
  keywords     = {{CD206; CD86; chemokines; EMR1; epithelial cell markers}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{209--223}},
  publisher    = {{Springer}},
  series       = {{Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}},
  title        = {{The myeloid cell biomarker EMR1 is ectopically expressed in colon cancer}},
  url          = {{http://dx.doi.org/10.3233/TUB-200082}},
  doi          = {{10.3233/TUB-200082}},
  volume       = {{43}},
  year         = {{2021}},
}