Research: CD44 isoforms and their interactomes: effects on melanoma
2021-2022 PhD Student in Morfogenesis and Tissue Engineering at University La Sapienza - Rome, Italy
2020-2021 Third Level Employee at Lifebrain S.r.l. - Guidonia Montecelio, Rome, Italy
2017-2019 Master's Degree in Genomic Biotechnology at University La Sapienza - Rome, Italy
2014-2017 Bachelor's Degree in Agroindustrial Biotechnology at University La Sapienza - Rome, Italy
2014 P.N.I. Scientific High School Diploma at the Nomentano State Scientific High School- Rome, Italy
Summary of the research project
My project aims to clarify the role of specific ligand-CD44 isoforms interactions and the effects of these interactions on the
characteristic features of melanoma, with particular interest to the effects of the interaction with important ligands, including
hyaluronic acid. The ability of melanoma cells to migrate and spread beyond the primary site of the tumor is strongly enhanced by the expression of surface molecules, which mediate cell-cell and cell-extracellular matrix interactions. Among these, CD44, the main surface receptor for hyaluronic acid (HA), plays a crucial role in invasion and metastatic processes, in various human cancers including melanoma. Growing evidence suggests that CD44 is extensively overexpressed in numerous types of cancer and that it correlates with aggressive biological behavior and a poor prognosis. CD44 is involved in the epithelial-mesenchymal transition process in melanoma, as in many other cancers, and is recognized as a marker for cancer stem cells in gastric and breast cancer; it is also involved in drug resistance and resistance to radiotherapy and chemotherapy in different types of cancer. In melanoma the most interesting CD44 isoforms are CD44t6 and CD44t7, but numerous other combinations of variant exons are possible and their presence is attested in patients. All CD44 surface receptors have in the extracellular region a binding domain for HA; the binding results in a signal transduction involving multiple pathways, including the pathways of BRAF, MAPK/ERK, WNT. Most recent studies argue that tumors
expressing particular isoforms of CD44 are more aggressive and therefore exhibit characteristics, typical of tumors, more
exacerbated, compared to tumors that express only the more abundant isoform, namely CD44standard. However, the contribution of specific CD44 isoforms and their natural interactors, which are not limited to hyaluronic acid, has been little studied in melanoma. In this project we have included the study of osteopontins, versicans and few matrix metalloproteases. The aspects that the project intends to explore concern the effects of the interactions of these ligands with specific CD44 isoforms on the morphological changes of the cells and changes in the main signal transduction pathways. The proliferation, migration and invasion capacity of these cells will be evaluated. If these assays give significant results, we will proceed with in vivo assays to observe the contribution to metastases. The experimental model includes the human melanoma cell lines A375, CHL1, 501mel, already used in multiple studies, and the IGR37 and IGR39 cell lines, respectively primary and metastatic melanoma of a patient, of more recent availability. If the initial data are promising, we will include patient biopsies for immunohistochemical assays. With these investigations, I hope to identify a role in melanoma for the interaction between specific isoforms of the CD44 receptor and its main interactors, with the possibility of paving the way for targeted therapies or the use of these as early indicators of melanoma aggression capacity.