Assistant Professor
Department of Experimental and Clinical Biomedical Sciences University of Insubria,
via J.H. Dunant, 5 21100 Varese (VA) Italy
Tel:: +39-0332-217141
Fax: +39-0332-217119
E-mail: manuela.viola@uninsubria.it

The metabolism, turnover and modifications of the molecules of the extracellular matrix (glycosaminoglycans, metalloproteinases, collagens, proteoglycans etc). In particular, the studies of all the research group of biochemistry concerning the GAG hyaluronan in various normal and pathological conditions using tissues or cell cultures (see also the research interest of Prof De Luca, Prof. Passi and Dr Vigetti).

Dr Viola's main research focus is in hyaluronan metabolism in carcinoma, in fact, qualitative and quantitative changes are frequently observed in the extracellular matrix stroma surrounding cancer. High level of hyaluronan (HA) is often associated with malignant progression in many cancers, such as breast cancer, colorectal cancer, and glioma. Hyaluronan-rich matrices around tumors favor the cancer cells migration and infiltration of newly formed blood vessels.

Changes in hyaluronan content within primary tumors result from complex interactions between the carcer cells and associated stroma: growth factors and cytokines produced by the carcinoma may stimulate fibroblasts embedded in the stroma to increase the production of hyaluronan and associated hyaluronan-binding matrix components. Human breast cancer cell line 8701BC, expresses the enzymes involved in HA metabolism, the synthases HAS2 and 3 and the hyaluronidases; nevertheless cells do not produce HA in ECM but only few molecules of HA are evident within the cells.

In co-culture in Transwell system with fibroblasts and tumor cells it was evident that 8701BC cells and fibroblasts increased the expression of the HA synthases, demonstrating a cross-talk between these cells; further analysis are in progress to elucidate the molecules involved in this interaction. One particular proteoglycan, was reported to have an effect on decreasing the cancer growth, so the reported breast cancer cell line were transfected by a group of collaborator at the University of Pavia (Prof Tenni and Tira) in order to elucidate its role, in term of alteration of growth rate and ECM molecules surrounding BC cells.

Additional research in collaboration with Prof. Negrini and Dr. Moriondo concerns the evaluation of the alterations of ECM in lung tissues during spontaneous or mechanical ventilation; in particular the molecules mainly studied in that case are metalloproteinases, glycosaminoglycans and cytokines that are involved in the degradation of the tissue and subsequently in the insufficient tissue activity.

AS a result of the above reported research, new technique were developed and their results published, in particular the methodology for studies of glycosaminoglycans were improved: HPLC and FACE were described to separate and quantify the disaccharides belonging to hyaluronan and/or chondroitin and dermatan glycosaminoglycans.

Assistant Professor, Department of Experimental and Clinical Biomedical Sciences, University of Insubria.

Assistant Professor, School of Medicine, University of Insubria.

Courses Taught:
Biochemistry for the degree courses in Biomedical laboratory techniques, Obstetrics and Techniques of Cardiocirculatory Physiopathology and Cardiovascular Perfusion.
Extracellular matrix and tumour for the School of Medicine