Biophysical Parameters Can Induce Epithelial-to-Mesenchymal Phenotypic and Genotypic Changes in HT-29 Cells: A...

Area of Science:

• Cancer Biology
• Biophysics
• Cellular Microenvironment

Background:

• Epithelial to mesenchymal transition (EMT) enhances cancer cell invasiveness.
• Current 3D cancer models often fail to replicate the native tumor microenvironment crucial for EMT.
• Understanding microenvironment's role in EMT is key for developing effective cancer therapies.

Purpose of the Study:

• To investigate how oxygen levels and collagen matrix stiffness influence invasion and EMT in HT-29 colorectal cancer cells.
• To compare the response of HT-29 cells to microenvironmental factors with a pre-EMT mesenchymal cell line (MDA-MB-231).

Main Methods:

• Cultured HT-29 colorectal cells in 2D and 3D collagen matrices (soft and stiff) under varying oxygen conditions (hypoxia and normoxia).
• Assessed EMT marker expression and invasion patterns.
• Analyzed expression of invasion-related genes (MMP2, RAE1).

Main Results:

• Physiological hypoxia induced EMT markers in HT-29 cells in 2D cultures.
• HT-29 cells exhibited increased invasion in stiff 3D matrices, irrespective of oxygen levels.
• Stiffness of the 3D matrix significantly enhanced HT-29 cell invasion and expression of MMP2 and RAE1 genes.

Conclusions:

• The biophysical microenvironment, particularly matrix stiffness, directly impacts cancer cell behavior and invasion.
• HT-29 cells are sensitive to microenvironmental cues, unlike pre-EMT cell lines like MDA-MB-231.
• This study underscores the importance of biomimetic 3D models for studying cancer progression and EMT.