Spatial Organisation and Invasive Behaviour of Metastatic Cutaneous Squamous Cell Carcinoma-Derived Multicellular...

Area of Science:

• Oncology
• Cell Biology
• Cancer Research

Background:

• Cutaneous squamous cell carcinoma (cSCC) is a common head and neck cancer with metastatic potential.
• Epithelial-to-mesenchymal transition (EMT) and cancer-associated fibroblasts (CAFs) are key drivers of cancer progression.
• Understanding tumor-stroma interactions is crucial for developing effective treatments.

Purpose of the Study:

• To develop and characterize multicellular tumor spheroids (MCTS) using patient-derived metastatic cSCC cell lines and fibroblasts.
• To investigate how different combinations of cSCC cells and fibroblasts influence MCTS formation, architecture, and invasion.
• To explore the relationship between cancer cell EMT phenotype and invasive behavior within MCTS models.

Main Methods:

• Live-cell microscopy was used to assess spatial architectures of MCTS.
• Expression of EMT and CAF markers was evaluated.
• MCTS were utilized in invasion models to study invasion modes and their association with cancer cell EMT phenotype.

Main Results:

• Metastatic cSCC/fibroblast MCTS self-organized into distinct spatial architectures.
• MCTS invasion through collagen was influenced by fibroblasts but predominantly determined by the EMT status of the cancer cells.
• A clear association was observed between the mode of invasion and the EMT phenotype of the cSCC cell line.

Conclusions:

• MCTS serve as a physiologically relevant model for studying tumor-stroma interactions in metastatic cSCC.
• The EMT status of cancer cells is a dominant factor in determining invasion dynamics.
• These findings offer insights into the mechanisms of cSCC metastasis and potential therapeutic targets.