Human Prostate Tissue-derived Extracellular Matrix as a Model of Prostate Microenvironment

Abstract

BackgroundClinical experience highlights the wide heterogeneity of primary prostate cancer (PPCa), even when potentially related to the same grade and stage. Currently available prediction tools and biomarkers do not always allow for early recognition of PPCa aggressive phenotype, sometimes making it impossible to distinguish among men harbouring indolent tumours or life-threatening disease. ObjectiveTo establish a novel ex vivo/in vitro model suitable to estimate the invasive phenotype of PPCa cells (PPCaC). Design, setting, and participantsThe ability of PPCaC to infiltrate the prostate extracellular matrix (ECM) was used as an index of invasion. ECM was obtained by decellularising 24 NT-prostate specimens from radical prostatectomy. PPCaC were obtained from six tumours with different Gleason patterns and pathological stages. Invasion ability was estimated in direct-cocolture experiments. Outcome measurements and statistical analysisThe extent of ECM invasion by PPCaC was quantified by counting the number of infiltrated cells. Mann–Whitney test was utilised for statistical comparisons. Results and limitationsSamples of ECM resulted to be free of cells and DNA and with a preserved three-dimensional structure and stromal protein content. The system resulted to be reliable since well characterised normal-, benign-, and malignant-prostate cell lines either re-epitheliased or invaded the matrices, according to their specific nature. Similarly, PPCaC invaded the ECMs consistently with their stage and biochemical recurrence. Of notice, this model was able to identify a different invasive phenotype even among tumours with equal Gleason patterns and pathological stages. The small sample size represents a limitation. ConclusionsWe developed an ex vivo/in vitro model able to reproduce the original PPCa-microenvironment and suitable to recognise the inherent invasive behaviour of PPCaC. Patient summaryWe developed a novel ex vivo/in vitro system which enables us to uncover which prostate tumours host potentially aggressive cancer cells. The identification of cancer cells with different invasive abilities will likely lead to the identification of new biomarkers to safely predict disease progression.