CXCL12 is expressed by skeletal muscle cells in tongue oral squamous cell carcinoma

Abstract Background The CXCL12/CXCR4 axis plays a pivotal role in the progression of various malignancies, including oral squamous cell carcinoma (OSCC). In this study, we aimed to clarify the biological and clinical significance of CXCL12 in the tumor microenvironment of OSCCs. Methods Publicly ava...

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Main Authors: Akira Yorozu, Shohei Sekiguchi, Akira Takasawa, Fumika Okazaki, Takeshi Niinuma, Hiroshi Kitajima, Eiichiro Yamamoto, Masahiro Kai, Mutsumi Toyota, Yui Hatanaka, Koyo Nishiyama, Kazuhiro Ogi, Hironari Dehari, Kazufumi Obata, Makoto Kurose, Atsushi Kondo, Makoto Osanai, Akihiro Miyazaki, Kenichi Takano, Hiromu Suzuki
Format: Article
Language:English
Published: Wiley 2023-03-01
Series:Cancer Medicine
Subjects:
Online Access:https://doi.org/10.1002/cam4.5392
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author Akira Yorozu
Shohei Sekiguchi
Akira Takasawa
Fumika Okazaki
Takeshi Niinuma
Hiroshi Kitajima
Eiichiro Yamamoto
Masahiro Kai
Mutsumi Toyota
Yui Hatanaka
Koyo Nishiyama
Kazuhiro Ogi
Hironari Dehari
Kazufumi Obata
Makoto Kurose
Atsushi Kondo
Makoto Osanai
Akihiro Miyazaki
Kenichi Takano
Hiromu Suzuki
author_facet Akira Yorozu
Shohei Sekiguchi
Akira Takasawa
Fumika Okazaki
Takeshi Niinuma
Hiroshi Kitajima
Eiichiro Yamamoto
Masahiro Kai
Mutsumi Toyota
Yui Hatanaka
Koyo Nishiyama
Kazuhiro Ogi
Hironari Dehari
Kazufumi Obata
Makoto Kurose
Atsushi Kondo
Makoto Osanai
Akihiro Miyazaki
Kenichi Takano
Hiromu Suzuki
author_sort Akira Yorozu
collection DOAJ
description Abstract Background The CXCL12/CXCR4 axis plays a pivotal role in the progression of various malignancies, including oral squamous cell carcinoma (OSCC). In this study, we aimed to clarify the biological and clinical significance of CXCL12 in the tumor microenvironment of OSCCs. Methods Publicly available single‐cell RNA‐sequencing (RNA‐seq) datasets were used to analyze CXCL12 expression in head and neck squamous cell carcinomas (HNSCC). Immunohistochemical analysis of CXCL12, α‐smooth muscle antigen (α‐SMA), fibroblast activation protein (FAP) and CD8 was performed in a series of 47 surgically resected primary tongue OSCCs. Human skeletal muscle cells were co‐cultured with or without OSCC cells, after which CXCL12 expression was analyzed using quantitative reverse‐transcription PCR. Results Analysis of the RNA‐seq data suggested CXCL12 is abundantly expressed in stromal cells within HNSCC tissue. Immunohistochemical analysis showed that in grade 1 primary OSCCs, CXCL12 is expressed in both tumor cells and muscle cells. By contrast, grade 3 tumors were characterized by disruption of muscle structure and reduced CXCL12 expression. Quantitative analysis of CXCL12‐positive areas within tumors revealed that reduced CXCL12 expression correlated with poorer overall survival. Levels of CXCL12 expression tended to inversely correlate α‐SMA expression and positively correlate with infiltration by CD8+ lymphocytes, though these relations did not reach statistical significance. CXCL12 was significantly upregulated in muscle cells co‐cultured with OSCC cells. Conclusion Our results suggest that tongue OSCC cells activate CXCL12 expression in muscle cells, which may contribute to tumor progression. However, CXCL12 is reduced in advanced OSCCs due to muscle tissue destruction.
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spelling doaj.art-438974de98e1444292b4d87dce47cdcb2023-03-21T05:20:40ZengWileyCancer Medicine2045-76342023-03-011255953596310.1002/cam4.5392CXCL12 is expressed by skeletal muscle cells in tongue oral squamous cell carcinomaAkira Yorozu0Shohei Sekiguchi1Akira Takasawa2Fumika Okazaki3Takeshi Niinuma4Hiroshi Kitajima5Eiichiro Yamamoto6Masahiro Kai7Mutsumi Toyota8Yui Hatanaka9Koyo Nishiyama10Kazuhiro Ogi11Hironari Dehari12Kazufumi Obata13Makoto Kurose14Atsushi Kondo15Makoto Osanai16Akihiro Miyazaki17Kenichi Takano18Hiromu Suzuki19Department of Otolaryngology‐Head and Neck Surgery Sapporo Medical University School of Medicine Sapporo JapanDepartment of Molecular Biology Sapporo Medical University School of Medicine Sapporo JapanDepartment of Pathology Sapporo Medical University School of Medicine Sapporo JapanDepartment of Molecular Biology Sapporo Medical University School of Medicine Sapporo JapanDepartment of Molecular Biology Sapporo Medical University School of Medicine Sapporo JapanDepartment of Molecular Biology Sapporo Medical University School of Medicine Sapporo JapanDepartment of Molecular Biology Sapporo Medical University School of Medicine Sapporo JapanDepartment of Molecular Biology Sapporo Medical University School of Medicine Sapporo JapanDepartment of Molecular Biology Sapporo Medical University School of Medicine Sapporo JapanDepartment of Molecular Biology Sapporo Medical University School of Medicine Sapporo JapanDepartment of Oral Surgery Sapporo Medical University School of Medicine Sapporo JapanDepartment of Oral Surgery Sapporo Medical University School of Medicine Sapporo JapanDepartment of Oral Surgery Sapporo Medical University School of Medicine Sapporo JapanDepartment of Otolaryngology‐Head and Neck Surgery Sapporo Medical University School of Medicine Sapporo JapanDepartment of Otolaryngology‐Head and Neck Surgery Sapporo Medical University School of Medicine Sapporo JapanDepartment of Otolaryngology‐Head and Neck Surgery Sapporo Medical University School of Medicine Sapporo JapanDepartment of Pathology Sapporo Medical University School of Medicine Sapporo JapanDepartment of Oral Surgery Sapporo Medical University School of Medicine Sapporo JapanDepartment of Otolaryngology‐Head and Neck Surgery Sapporo Medical University School of Medicine Sapporo JapanDepartment of Molecular Biology Sapporo Medical University School of Medicine Sapporo JapanAbstract Background The CXCL12/CXCR4 axis plays a pivotal role in the progression of various malignancies, including oral squamous cell carcinoma (OSCC). In this study, we aimed to clarify the biological and clinical significance of CXCL12 in the tumor microenvironment of OSCCs. Methods Publicly available single‐cell RNA‐sequencing (RNA‐seq) datasets were used to analyze CXCL12 expression in head and neck squamous cell carcinomas (HNSCC). Immunohistochemical analysis of CXCL12, α‐smooth muscle antigen (α‐SMA), fibroblast activation protein (FAP) and CD8 was performed in a series of 47 surgically resected primary tongue OSCCs. Human skeletal muscle cells were co‐cultured with or without OSCC cells, after which CXCL12 expression was analyzed using quantitative reverse‐transcription PCR. Results Analysis of the RNA‐seq data suggested CXCL12 is abundantly expressed in stromal cells within HNSCC tissue. Immunohistochemical analysis showed that in grade 1 primary OSCCs, CXCL12 is expressed in both tumor cells and muscle cells. By contrast, grade 3 tumors were characterized by disruption of muscle structure and reduced CXCL12 expression. Quantitative analysis of CXCL12‐positive areas within tumors revealed that reduced CXCL12 expression correlated with poorer overall survival. Levels of CXCL12 expression tended to inversely correlate α‐SMA expression and positively correlate with infiltration by CD8+ lymphocytes, though these relations did not reach statistical significance. CXCL12 was significantly upregulated in muscle cells co‐cultured with OSCC cells. Conclusion Our results suggest that tongue OSCC cells activate CXCL12 expression in muscle cells, which may contribute to tumor progression. However, CXCL12 is reduced in advanced OSCCs due to muscle tissue destruction.https://doi.org/10.1002/cam4.5392CXCL12muscle cellsOSCCprognosis
spellingShingle Akira Yorozu
Shohei Sekiguchi
Akira Takasawa
Fumika Okazaki
Takeshi Niinuma
Hiroshi Kitajima
Eiichiro Yamamoto
Masahiro Kai
Mutsumi Toyota
Yui Hatanaka
Koyo Nishiyama
Kazuhiro Ogi
Hironari Dehari
Kazufumi Obata
Makoto Kurose
Atsushi Kondo
Makoto Osanai
Akihiro Miyazaki
Kenichi Takano
Hiromu Suzuki
CXCL12 is expressed by skeletal muscle cells in tongue oral squamous cell carcinoma
Cancer Medicine
CXCL12
muscle cells
OSCC
prognosis
title CXCL12 is expressed by skeletal muscle cells in tongue oral squamous cell carcinoma
title_full CXCL12 is expressed by skeletal muscle cells in tongue oral squamous cell carcinoma
title_fullStr CXCL12 is expressed by skeletal muscle cells in tongue oral squamous cell carcinoma
title_full_unstemmed CXCL12 is expressed by skeletal muscle cells in tongue oral squamous cell carcinoma
title_short CXCL12 is expressed by skeletal muscle cells in tongue oral squamous cell carcinoma
title_sort cxcl12 is expressed by skeletal muscle cells in tongue oral squamous cell carcinoma
topic CXCL12
muscle cells
OSCC
prognosis
url https://doi.org/10.1002/cam4.5392
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