PMID- 31088266
OWN - NLM
STAT- MEDLINE
DCOM- 20191220
LR  - 20230719
IS  - 1533-0338 (Electronic)
IS  - 1533-0346 (Print)
IS  - 1533-0338 (Linking)
VI  - 18
DP  - 2019 Jan 1
TI  - Colon Cancer Cell Secretes EGF to Promote M2 Polarization of TAM Through 
      EGFR/PI3K/AKT/mTOR Pathway.
PG  - 1533033819849068
LID - 10.1177/1533033819849068 [doi]
LID - 1533033819849068
AB  - BACKGROUND: Tumor environment has been recognized to affect cancer cell 
      progression, such as tumor-associated macrophages. However, increasing evidences 
      suggest that tumor cells are capable of regulating polarization of 
      tumor-associated macrophages. In this study, we investigate the mechanism of how 
      colon cancer cell impacts tumor-associated macrophages polarization. METHODS: We 
      employed flow cytometry to detect marker molecules on macrophage membrane, such 
      as CD68, CD16, and CD204. In addition, we used enzyme-linked immunosorbent assay 
      to examine the level of these cytokines (interleukin-6, interleukin-1beta, 
      interleukin-10, and Arginase-1) secreted by colon cancer cells into the culture 
      medium. Western blot was utilized to probe downstream proteins of epidermal 
      growth factor receptor (EGFR)/phosphoinositide 3-kinase (PI3K)/protein kinase B 
      (AKT)/mammalian target of rapamycin (mTOR) pathway. RESULTS: We cocultured colon 
      cancer cell lines (HCT8 or HCT116) with human myeloid leukemia mononuclear cells 
      (THP-1) and found that interleukin-6 and interleukin-1beta levels were reduced, and 
      instead, interleukin-10 and Arginase-1 levels were elevated, suggesting that 
      colon cancer cells contributed to M2 polarization of THP-1. Meanwhile, high level 
      of various growth factors (transforming growth factor-beta [TGF-beta], epidermal growth 
      factor [EGF], and hepatocyte growth factor [HGF]) was observed in the medium of 
      THP-1 cocultured with colon cancer cells. Furthermore, the protein level of 
      phosphorylated PI3K, AKT, and mTOR significantly increased in THP-1 cell 
      cocultured with colon cancer cells compared to THP-1 group. Besides, we 
      established that colon cancer cells exerted their stimulatory effect on M2 
      polarization of macrophage from monocyte THP-1 using EGFR antibody mAb225 and 
      PI3K inhibitor LY294002. CONCLUSION: We provide evidence that EGF which are 
      secreted by colon cancer cells play contributory role in M2 polarization of 
      macrophages, which support the notion that tumor environment, including 
      tumor-associated macrophages, can be targeted to develop effective strategies for 
      treating cancer.
FAU - Lian, Guanghui
AU  - Lian G
AD  - 1 Department of Gastroenterology, Xiangya Hospital, Central South University, 
      Changsha, People's Republic of China.
FAU - Chen, Shuijiao
AU  - Chen S
AD  - 1 Department of Gastroenterology, Xiangya Hospital, Central South University, 
      Changsha, People's Republic of China.
FAU - Ouyang, Miao
AU  - Ouyang M
AD  - 1 Department of Gastroenterology, Xiangya Hospital, Central South University, 
      Changsha, People's Republic of China.
FAU - Li, Fujun
AU  - Li F
AD  - 1 Department of Gastroenterology, Xiangya Hospital, Central South University, 
      Changsha, People's Republic of China.
FAU - Chen, Linlin
AU  - Chen L
AD  - 1 Department of Gastroenterology, Xiangya Hospital, Central South University, 
      Changsha, People's Republic of China.
FAU - Yang, Junwen
AU  - Yang J
AUID- ORCID: 0000-0002-4740-1181
AD  - 1 Department of Gastroenterology, Xiangya Hospital, Central South University, 
      Changsha, People's Republic of China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Technol Cancer Res Treat
JT  - Technology in cancer research & treatment
JID - 101140941
RN  - 0 (Cytokines)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
EIN - Technol Cancer Res Treat. 2023 Jan-Dec;22:15330338231188082. PMID: 37464782
MH  - Cell Line, Tumor
MH  - Colonic Neoplasms/*metabolism
MH  - Cytokines/metabolism
MH  - Epidermal Growth Factor/*biosynthesis
MH  - ErbB Receptors/metabolism
MH  - Humans
MH  - Macrophage Activation
MH  - Macrophages/immunology/*metabolism/pathology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Protein Binding
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - *Signal Transduction
MH  - THP-1 Cells
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC6535704
OTO - NOTNLM
OT  - EGF/EGFR
OT  - M2 polarization
OT  - PI3K/AKT/mTOR pathway
OT  - colon cancer cell
OT  - macrophage
COIS- Declaration of Conflicting Interests: The author(s) declared no potential 
      conflicts of interest with respect to the research, authorship, and/or 
      publication of this article.
EDAT- 2019/05/16 06:00
MHDA- 2019/12/21 06:00
PMCR- 2019/05/14
CRDT- 2019/05/16 06:00
PHST- 2019/05/16 06:00 [entrez]
PHST- 2019/05/16 06:00 [pubmed]
PHST- 2019/12/21 06:00 [medline]
PHST- 2019/05/14 00:00 [pmc-release]
AID - 10.1177_1533033819849068 [pii]
AID - 10.1177/1533033819849068 [doi]
PST - ppublish
SO  - Technol Cancer Res Treat. 2019 Jan 1;18:1533033819849068. doi: 
      10.1177/1533033819849068.