A human multi-cellular model shows how platelets drive production of diseased extracellular matrix and tissue invasion

Guided by amulti-level deconstruction'' of omentalmetastases, we developed a tetra (four cell)-culture model of primary human mesothelial cells, fibroblasts, adipocytes, and high-grade serous ovarian cancer (HGSOC) cell lines. This multi-cellular model replicated key elements of human metastases and allowed malignant cell invasion into the artificial omental structure. Prompted by findings in patient biopsies, we used the model to investigate the role of platelets in malignant cell invasion and extracellular matrix, ECM, production. RNA (sequencing and quantitative polymerase-chain reaction), protein (proteomics and immuno-histochemistry) and image analysis revealed that platelets stimulated malignant cell invasion and production of ECM molecules associated with poor prognosis. Moreover, we found that platelet activation of mesothelial cells was critical in stimulating malignant cell invasion. Whilst platelets likely activate bothmalignant cells and mesothelial cells, the tetra-culture model allowed us to dissect the role of both cell types and model the early stages of HGSOC metastases.

Automated summary

The team developed a four-cell culture model to investigate the role of platelets in malignant cell invasion and extracellular matrix production, revealing their promotion of factors associated with poor prognosis. They found that platelet activation is critical in stimulating malignant cell invasion and successfully dissected the roles of malignant cells and mesothelial cells.