Ameloblastoma modifies tumor microenvironment for enhancing invasiveness by altering collagen alignment

Area of Science:

• Oncology
• Oral Pathology
• Biomaterials Science

Background:

• Tumor progression is influenced by cancer cell and stroma interactions within the tumor microenvironment (TME).
• Investigating the extracellular matrix (ECM) role in odontogenic epithelial neoplasms, specifically ameloblastoma, is crucial for understanding tumor progression.
• The mechanisms of ECM remodeling in ameloblastoma remain largely unelucidated.

Purpose of the Study:

• To investigate the role of the tumor microenvironment (TME) and extracellular matrix (ECM) in ameloblastoma progression.
• To elucidate the ECM remodeling mechanisms employed by ameloblastoma cells.
• To compare TME-related gene expression between ameloblastoma and odontogenic keratocysts.

Main Methods:

• Transcriptomic comparison of ameloblastoma and odontogenic keratocysts.
• Histopathologic analysis of tumor tissues.
• Tumoroid culture models to assess ECM interaction and remodeling.

Main Results:

• Upregulation of TME-related genes was observed in ameloblastoma compared to odontogenic keratocysts.
• Type I collagen was identified as essential for ameloblastoma progression.
• Ameloblastoma demonstrated an intrinsic capacity for ECM remodeling, independent of cancer-associated fibroblasts.

Conclusions:

• Ameloblastoma progression is characterized by significant ECM remodeling.
• The tumor actively remodels the ECM, forming an invasive collagen architecture.
• This ameloblastoma-mediated ECM remodeling is a key factor in tumor progression.