Defining the cell surface proteoglycan metastatic signature of cancer cells: role of Glypican-5 in the control of cell motility

Abstract

Surveying literature data, what emerges is that cellular function and phenotype are highly influenced by cell surface proteoglycans (PGs), present at the cell-tissue-organ interface where they are thought to have crucial regulatory roles in cellular control and in coordinating and directing appropriate response to multiple ligands in normal physiological processes and pathological conditions, including the processes of tumor onset and progression. The complexity of PG surface pattern in tumour cells, especially that provided by glypicans, syndecans and NG2, enables them to modulate directly or indirectly several aspects of the tumour cell phenotype, including growth kinetics, invasiveness and metastatic potential. Recent evidence further highlights the fact that cancer cells, as part of the transformation process, alter their cell surface PG profile, but also alters the fine structure of a given proteoglycans and the tumorigenic function of the 11 primary PGs, including syndecans-1-4, glypicans-1-6 and NG2, is only in part resolved for some of these PGs individually, but is obscure when considering these molecules cumulatively. In this context, we have focused our research on trying to understand how a given cell surface PG pattern may be involved in tumour growth and metastasis in sarcomas and whether they could represent new potential prognostic/predictive markers in defined class of patients with oral squamous cell carcinomas (OSCC). We have approached this problem defining systematically the constitutive pattern of cell surface PG expression in a large panel of sarcoma cells and OSCC biopsies combining analyses at the transcript and immunochemical level and by creating 143B osteosarcoma cells over-expressing glypican-5. This engineered cellular model was then assayed for its adhesion and migratory abilities in response to isolated molecules of the extracellular matrix in vitro. Misexpression of glypican-5 on defined constitutive PG backgrounds modulates the in vitro behavior of the cells. The outcome of this project could provide the preliminary evidence that defined surface PGs pattern could differentially control cancer cells behavior and could be a new perspective in the understanding how these molecules regulate different aspects of cancer biology.