Regulation of Tumor Growth and Invasion in Oral Squamous Cell Carcinoma by the Tumor Microenvironment Through the Enhancement of IGFBP-3 Expression.

IF 1.6 4区 医学 Q4 ONCOLOGY
Dokyeong Kim, Young Jin Park, Young Sun Hwang
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引用次数: 0

Abstract

Background/aim: Accumulated evidence indicates that interactions among various stromal cells within the tumor microenvironment (TME) significantly influence cancer progression. Oral cancers not diagnosed at early stages are associated with low five-year survival rates, highlighting the need for substantial improvements in patient outcomes. Understanding the interactions between cancer cells and the tumor microenvironment is crucial for identifying methods and developing treatment strategies that more effectively inhibit tumor progression and metastasis.

Materials and methods: This study investigated the roles of cancer-associated fibroblasts (CAFs) and THP-1 monocytes in tumor growth and invasion, observing changes in cancer biological characteristics through interactions with stromal cells. HSC2 oral squamous cell carcinoma (OSCC) cells were co-cultured with normal fibroblasts (NF), cancer-associated fibroblasts (CAF), or THP-1 cells. Changes in cancer cell invasion were investigated using Matrigel-coated transwell assays, collagen-based dermal equivalent assays, and in vivo mouse studies.

Results: HSC2 cells co-cultured with CAFs or THP-1 exhibited increased invasion compared to those co-cultured with normal fibroblasts (NF) in the dermal equivalent. In a mouse gingival xenograft model, cancer cells co-implanted with CAFs or THP-1 showed significantly increased tumor growth compared to those co-implanted with NF. Micro-CT (μCT) analysis revealed significant alveolar bone resorption around the mandible in tumors grown with CAFs or THP-1 cells. Conditioned media (CM) from CAFs or THP-1 significantly increased HSC2 invasion and migration, an effect that was inhibited by the protein secretion inhibitor Brefeldin (BFA). Furthermore, QuantSeq 3' mRNA sequencing indicated increased expression of IGFBP3, closely associated with cancer invasion, in HSC2 cells co-cultured with CAFs or THP-1.

Conclusion: These findings suggest that cancer cells enhance their invasive characteristics through close interactions with the surrounding stromal cells.

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来源期刊
Anticancer research
Anticancer research 医学-肿瘤学
CiteScore
3.70
自引率
10.00%
发文量
566
审稿时长
2 months
期刊介绍: ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed. ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies). Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.
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