Analysis of Prostate Fibroblast Derived Extracellular Matrix Proteins Unveils the Microenvironment Niche of Prostate Epithelial Stem Cells

The composition and the organization of extracellular matrix (ECM) participate in the formation of the niche for epithelial stem cells. During tumor development the stroma surrounding the cancer cells is activated and remodeled, which may have a significant influence on cancer stem cells, tumor progression and cell invasion. Fibroblasts and cancer associated fibroblasts (CAFs) are the main producers of ECM. In prostate epithelial/cancer stem cells are identified as CD44⁺, CD133⁺, α2β1 integrin ^high and androgen receptor negative cells (Collins, et al., 2005, Cancer Res.). Integrin α2β1 is a collagen receptor proposing that cell–collagen interaction is important for stem cell biology. Still, the function of specific ECM molecules and receptors in regulating prostate stem cells remains poorly understood.

Here, we have used primary cultures of prostate-derived fibroblastic cells, allowed them to generate ECM in the presence of ascorbic acid and analyzed the composition of the ECM using mass spectrometry. Fibroblasts originated from either normal (n=18) or cancerous tissue area (n=10). In both cases the most abundant proteins were tenascin, fibronectin and collagens VI, XII and XIV. Significantly increased levels of collagen III (p< 0,05; Student’s t-test) and Periostin (p< 0,05; Student’s t-test) were observed in CAF related ECM when compared to normal fibroblasts.

Further studies on the function of altered matrix proteins to integrin signaling in prostate stem cells are currently in progress.