Ionizing radiation-induced "zombie" carcinoma-associated fibroblasts with suppressed pro-radioresistance on OSCC cells

被引：6

作者：

Liu, Yangfan ^{[1
,2
,3
,4
]}

Wu, Yang ^{[1
,2
,3
,4
,5
]}

Yang, Miao ^{[1
,2
,3
,4
]}

Yang, Jin ^{[1
,2
,3
,4
]}

Tong, Ruizhan ^{[6
]}

Zhao, Wei ^{[1
,2
,3
,4
]}

Wu, Fanglong ^{[1
,2
,3
,4
]}

Tian, Yuan ^{[1
,2
,3
,4
]}

Li, Xiaoyu ^{[1
,4
]}

Luo, Jingjing ^{[1
,2
,3
,4
]}

Zhou, Hongmei ^{[1
,2
,3
,4
]}

机构：

[1] Sichuan Univ, State Key Lab Oral Dis, Chengdu 610041, Peoples R China

[2] Sichuan Univ, Natl Ctr Stomatol, Chengdu 610041, Peoples R China

[3] Sichuan Univ, Natl Clin Res Ctr Oral Dis, Chengdu 610041, Peoples R China

[4] Sichuan Univ, West China Hosp Stomatol, Chengdu 610041, Peoples R China

[5] Zhejiang Univ, Dept Gen Dent, Affiliated Hosp 2, Sch Med, Hangzhou, Peoples R China

[6] Sichuan Univ, West China Hosp, Dept Thorac Canc, Chengdu, Peoples R China

来源：

ORAL DISEASES | 2023年 / 29卷 / 02期

基金：

中国国家自然科学基金;

关键词：

carcinoma-associated fibroblasts; ionizing radiation; oral squamous cell carcinoma; radioresistance; senescence; zombie-like; CANCER-ASSOCIATED FIBROBLASTS; MESENCHYMAL TRANSITION; PROGRESSION; SENESCENCE; BIOLOGY;

D O I：

10.1111/odi.13979

中图分类号：

R78 [口腔科学];

学科分类号：

1003 ;

摘要：

Objectives This study was to investigate the effect of ionizing radiation (IR) on oral carcinoma-associated fibroblasts (CAFs) and to further explore subsequent effects of IR-induced "zombie" CAFs on oral squamous cell carcinoma (OSCC) cells. Materials and methods Three primary CAFs and one primary normal-associated fibroblasts (NAFs) were separated from human OSCC and normal oral mucosa tissues, identified by immunocytochemistry. Cells were exposed to IR by X-ray irradiator under different doses. The DNA damage, proliferation, and migration of irradiated CAFs were, respectively, detected by immunofluorescence and wound healing assay, while senescence was detected by beta-galactosidase staining. Finally, the effect of irradiated CAFs on biological behavior and radioresistance of Cal-27 cells were determined via assays mentioned above. Results Oral CAFs were sensitive to IR with DNA damage increasing and proliferation decreasing. 18 Gy IR could not kill oral CAFs but induce them to "zombies," with arrested proliferation, increased senescence, and reduced migration. "Zombie" CAFs (zCAFs) could enhance proliferation, migration, and invasion of Cal-27 cells, and show suppressed pro-radioresistance by reducing DNA damage and facilitating survival. Conclusions IR-induced zCAFs could continuously promote radioresistance of OSCC cells though being suppressed, suggesting the potential promoting effect on tumor relapse post-radiotherapy that needed further exploring.

引用

页码：563 / 573

页数：11