期刊
CANCERS
卷 13, 期 13, 页码 -出版社
MDPI
DOI: 10.3390/cancers13133361
关键词
HNSCC; cancer-associated fibroblasts; cDNA microarray; MMP9; FMOD; overall survival
类别
资金
- Swedish Cancer Society [2017/301, 2020/0738]
- County Council of Ostergotland
- Research Funds of Linkoping University Hospital
- Cancer Foundation of Ostergotland
Cancer-associated fibroblasts (CAFs) alter the expression of multiple genes in HNSCC tumor cells, some of which are associated with proliferation, differentiation, and metastasis. The CAF-regulated genes MMP9 and FMOD are significantly associated with overall survival (OS) in patients treated with radiotherapy.
Simple Summary Cancer-associated fibroblasts (CAFs) are the major cellular component of the tumor microenvironment and have been shown to stimulate tumor growth, epithelial-to-mesenchymal transition (EMT), invasion, and radio-resistance. Radio-resistance leading to disease relapse is one of the major challenges in long-term survival and outcome in head and neck squamous cell carcinoma (HNSCC). Therefore, it is essential to search for predictive markers and new targets for treatment using clinically relevant in vitro tumor models. We show that CAFs alter the expression of HNSCC tumor cell genes, many of which are associated with proliferation, differentiation, and metastasis. Moreover, the expression pattern of selected CAF-regulated genes differed between HNSCC tumor tissue and the adjacent non-tumoral tissue. Two CAF-regulated genes, MMP9 and FMOD, were found to be associated with overall survival (OS) in patients treated with radiotherapy. Cancer-associated fibroblasts (CAFs) are known to increase tumor growth and to stimulate invasion and metastasis. Increasing evidence suggests that CAFs mediate response to various treatments. HNSCC cell lines were co-cultured with their patient-matched CAFs in 2D and 3D in vitro models, and the tumor cell gene expression profiles were investigated by cDNA microarray and qRT-PCR. The mRNA expression of eight candidate genes was examined in tumor biopsies from 32 HNSCC patients and in five biopsies from normal oral tissue. Differences in overall survival (OS) were tested with Kaplan-Meier long-rank analysis. Thirteen protein coding genes were found to be differentially expressed in tumor cells co-cultured with CAFs in 2D and 81 in 3D when compared to tumor cells cultured without CAFs. Six of these genes were upregulated both in 2D and 3D (POSTN, GREM1, BGN, COL1A2, COL6A3, and COL1A1). Moreover, two genes upregulated in 3D, MMP9 and FMOD, were significantly associated with the OS. In conclusion, we demonstrated in vitro that CAF-derived signals alter the tumor cell expression of multiple genes, several of which are associated with differentiation, epithelial-to-mesenchymal transition (EMT) phenotype, and metastasis. Moreover, six of the most highly upregulated genes were found to be overexpressed in tumor tissue compared to normal tissue.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据