Patient-Derived Colorectal Cancer Extracellular Matrices Modulate Cancer Cell Stemness Markers.

Area of Science:

• Cancer Biology
• Extracellular Matrix Research
• Stem Cell Science

Background:

• The tumor extracellular matrix (ECM) is known to support the cancer stem cell (CSC) niche.
• However, its specific role in modulating CSC properties is not well understood.

Purpose of the Study:

• To investigate how tumor ECM influences CSC properties.
• To evaluate the potential of patient-derived decellularized matrices as a model for studying stemness.

Main Methods:

• Decellularization and recellularization of paired normal and tumor colon tissues with colon cancer cells (HT-29, HCT-15).
• Analysis of stemness gene expression (NANOG, SOX2, OCT4, SNAI1) via qRT-PCR and flow cytometry.
• Quantification of TGF-β secretion and MMP activity using ELISA and zymography.
• Correlation of gene expression with patient survival data.

Main Results:

• Tumor decellularized matrices significantly enhanced NANOG, SOX2, OCT4, and SNAI1 expression in HT-29 cells compared to normal matrices.
• This was associated with increased expression of stemness receptors (CD44, CD133, CD166) and elevated secretion of TGF-β, MMP-2, and MMP-9.
• Higher expression of these stemness genes in patient cohorts correlated with worse overall survival.

Conclusions:

• Normal and tumor matrices exhibit distinct stemness-promoting potentials.
• Patient-derived decellularized matrices serve as a valuable 3D model for uncovering stemness signatures.
• Identified stemness-associated genes may represent targets for future colon cancer therapies.