TY - JOUR
T1 - CD206+ tumor-associated macrophages promote proliferation and invasion in oral squamous cell carcinoma via EGF production
AU - Haque, A. S.M.Rafiul
AU - Moriyama, Masafumi
AU - Kubota, Keigo
AU - Ishiguro, Noriko
AU - Sakamoto, Mizuki
AU - Chinju, Akira
AU - Mochizuki, Keita
AU - Sakamoto, Taiki
AU - Kaneko, Naoki
AU - Munemura, Ryusuke
AU - Maehara, Takashi
AU - Tanaka, Akihiko
AU - Hayashida, Jun Nosuke
AU - Kawano, Shintaro
AU - Kiyoshima, Tamotsu
AU - Nakamura, Seiji
N1 - Funding Information:
We would like to thank the Research Support Center, Research Center for Human Disease Modeling, Kyushu University Graduate School of Medical Sciences for the technical assistance. And we also appreciate Edanz Group (www.edanzediting.com/ac) for editing a draft of this article. Study conception and design: A.S.M.R.H., M.M., K.K. and S.N. Data acquisition: N.I., A.C., K.M., N.K., T.M. Quality control of data and algorithms: A.S.M.R.H., K.K. and M.S. Data analysis and interpretation: M.M., T.S., S.K. and T.K. Statistical analysis: R.M., T.M., A.T. and J.-N.H. Manuscript preparation and review: M.M. This work was supported by the Japan Society for the Promotion of Science [Grant Numbers 17H04671, 17H01603, 26293430] and “Practical Research Project for Rare/Intractable Diseases,” a matching fund subsidy from the Japan Agency for Medical Research and Development [Grant Number 17ek0109226h0001].
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Tumor-associated macrophages (TAMs) promote tumor progression and inhibit anti-tumor immune response by producing various mediators and preferentially express CD163, CD204, and CD206. However, the role of these TAM subsets in oral squamous cell carcinoma (OSCC) remains unclear. Here we investigated the expression and function of TAM subsets in OSCC, especially in cancer cell proliferation. Biopsy sample from 44 patients with OSCC were examined for the expression of TAM markers and EGF by immunohistochemistry. EGF production of TAM subsets isolated from OSCC patients was assessed by flow cytometry. We also examined the effect of conditioned medium from TAM subsets on the proliferation of OSCC cells. CD163+ cells were detected diffusely all over the tumor and connective tissue area, while CD204+ and CD206+ cells were mainly detected in/around the tumors. Flow cytometric analysis found that CD206+ TAMs strongly produced EGF compared with CD163+ and CD204+ TAMs. Cell proliferation and invasion of OSCC cells cultured with conditioned medium of CD206+ TAMs were strongly enhanced and inhibited by anti-EGFR. The number of CD206+ TAMs positively correlated with worse clinical prognosis. Our results revealed differences in localization and EGF production among these TAM subsets. CD206+ TAMs might play a critical role in the proliferation of OSCC via EGF production.
AB - Tumor-associated macrophages (TAMs) promote tumor progression and inhibit anti-tumor immune response by producing various mediators and preferentially express CD163, CD204, and CD206. However, the role of these TAM subsets in oral squamous cell carcinoma (OSCC) remains unclear. Here we investigated the expression and function of TAM subsets in OSCC, especially in cancer cell proliferation. Biopsy sample from 44 patients with OSCC were examined for the expression of TAM markers and EGF by immunohistochemistry. EGF production of TAM subsets isolated from OSCC patients was assessed by flow cytometry. We also examined the effect of conditioned medium from TAM subsets on the proliferation of OSCC cells. CD163+ cells were detected diffusely all over the tumor and connective tissue area, while CD204+ and CD206+ cells were mainly detected in/around the tumors. Flow cytometric analysis found that CD206+ TAMs strongly produced EGF compared with CD163+ and CD204+ TAMs. Cell proliferation and invasion of OSCC cells cultured with conditioned medium of CD206+ TAMs were strongly enhanced and inhibited by anti-EGFR. The number of CD206+ TAMs positively correlated with worse clinical prognosis. Our results revealed differences in localization and EGF production among these TAM subsets. CD206+ TAMs might play a critical role in the proliferation of OSCC via EGF production.
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U2 - 10.1038/s41598-019-51149-1
DO - 10.1038/s41598-019-51149-1
M3 - Article
C2 - 31601953
AN - SCOPUS:85073118218
SN - 2045-2322
VL - 9
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 14611
ER -