Polarization of tumor-associated macrophages and Gas6/Axl signaling in oral squamous cell carcinoma

Kuo-Chou Chiu; Chien-Hsing Lee; Shyun-Yeu Liu; Yu-Ting Chou; Ren-Yeong Huang; Shih-Ming Huang; Yi-Shing Shieh

doi:10.1016/j.oraloncology.2015.04.004

Polarization of tumor-associated macrophages and Gas6/Axl signaling in oral squamous cell carcinoma

Oral Oncol. 2015 Jul;51(7):683-9. doi: 10.1016/j.oraloncology.2015.04.004. Epub 2015 Apr 21.

Authors

Kuo-Chou Chiu¹, Chien-Hsing Lee², Shyun-Yeu Liu³, Yu-Ting Chou⁴, Ren-Yeong Huang⁵, Shih-Ming Huang⁶, Yi-Shing Shieh⁷

Affiliations

¹ Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan; Department of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
² Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
³ Department of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Oral & Maxillofacial Surgery, ChiMei Medical Center, Tainan, Taiwan.
⁴ Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan.
⁵ Department of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
⁶ Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
⁷ Department of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan. Electronic address: ndmcyss@mail.ndmctsgh.edu.tw.

PMID: 25910588
DOI: 10.1016/j.oraloncology.2015.04.004

Abstract

Background: This study investigated the potential involvement of Axl signaling in polarization of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC).

Methods: Condition medium (CM) from OSCC cells (OEC-M1 and YD38) were collected and their effects on macrophage (THP-1) polarization were examined. Modulation of Axl, PI3/Akt, and NF-κB were performed to investigate their potential involvement in TAM polarization. Expression of pAxl and CD206 were analyzed by immunohistochemistry in OSCC tissues.

Results: THP-1 polarized to M2 phenotype with increasing expression of interleukins, vascular endothelial growth factor, matrix metalloproteinase and CD206 upon treatment with CM of OSCC. Activated Axl signaling in OSCC enhanced M2 induction ability. Suppression of Axl signaling and inhibition of PI3/Akt and NF-κB diminished M2 induction. pAxl expression was significantly associated with distribution of CD206 positive cells in OSCC tissues.

Conclusion: Axl signaling of OSCC involved in polarizing TAMs toward M2 phenotype. Induction of M2 phenotype macrophage polarization by OSCC cells might involve the Axl/PI3/Akt/NF-κB pathway.

Keywords: Axl; Microenvironment; Oral squamous cell carcinoma; Tumor-associated macrophage.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Axl Receptor Tyrosine Kinase
Carcinoma, Squamous Cell / metabolism*
Cell Line, Tumor
Humans
Interleukins / metabolism
Lectins, C-Type / metabolism
Macrophages / metabolism*
Mannose Receptor
Mannose-Binding Lectins / metabolism
Matrix Metalloproteinases / metabolism
Mouth Neoplasms / metabolism*
NF-kappa B / metabolism
Proto-Oncogene Proteins / metabolism
Receptor Protein-Tyrosine Kinases / metabolism
Receptors, Cell Surface / metabolism
Signal Transduction
Vascular Endothelial Growth Factor A / metabolism

Substances

Interleukins
Lectins, C-Type
Mannose Receptor
Mannose-Binding Lectins
NF-kappa B
Proto-Oncogene Proteins
Receptors, Cell Surface
Vascular Endothelial Growth Factor A
Receptor Protein-Tyrosine Kinases
Matrix Metalloproteinases
Axl Receptor Tyrosine Kinase
AXL protein, human