Title: MMP-20 Expression in 3D-Ex-Vivo Cancer-Bone Interactive Model Systems
Melissa Ferguson (Presenter)
Serge Dibart, Boston University
Erdjan Salih, Boston University
Objectives: Matrix Metalloprotease (MMP)-20 is a proteolytic enzyme previously thought to be restricted to enamel formation and development. Recent studies have found that MMP-20 is expressed in different body tissues and interestingly, found to be increased in cancer pathology. Aggressive cancers can metastasize to bone marking the untreatable and terminal state of the disease. The objective of this study is to investigate MMP-20 protein expression in tumor cell lines interacting with bone in an ex-vivo live bone and cancer cell co-culture system.
Methods: We have utilized 3D co-culture dynamic model system with live mouse calvarial bones and cancer cells under dissociated bone remodeling stages, viz., osteoblastic bone formation or osteoclastic bone resorption, to identify the novel effects of cancer-bone interactions on MMP-20 expression. Oral Squamous Carcinoma cell line (OSCC) and two breast cancer cell lines were investigated; MDA-MB-231 and a more aggressive/bone seeking MDA-BO tumor cell line, using human and mouse specific ELISA.
Results: Our study found an increase in MMP-20 expression secreted from all tumor cell types interacting with live calvarial bones in an osteoclastic differentiated state compared to calvaria in an osteoblastic differentiated state. MDA-BO is found to have an increased MMP20 expression compared to the less aggressive tumor cell lines. The cell lines MDA-MB-231 and MBA-BO have MMP20 protein expressed which were previously not investigated or found to contain MMP20. The last novel finding of our study is that live ex-vivo calvarial bones have an inherently high expression of MMP20 protein regardless of formation or resorption status.
Conclusions: In conclusion, our study offers support to previous studies that suggest MMP20 effects cancer prognosis and aggressiveness with our studies’ novel finding that the more aggressive breast cancer cell line had increased MMP20 expression. Further studies are warranted to investigate MMP20’s role in more aggressive cell lines in a bone/cancer co-culture system.