Thesis defence in the University of Oulu

Doctoral Candidate

DDS Otto Väyrynen

Faculty and research unit

University of Oulu Graduate School, Faculty of Medicine, Cancer and Translational Medicine Research Unit

Field of study

Diagnostics and Oral Medicine

Date and time of the thesis defence

14.6.2019 12:00

Place of the thesis defence

Seminar room 3, Biomedical 1, Haartmaninkatu 8, 00290 Helsinki

Topic of the dissertation

Factors affecting aggressive oral tongue cancer invasion and development of in vitro models for chemoradiotherapy assay

Opponent

Docent Tero Soukka, Turku University Hospital, Department of Oral and Maxillofacial Diseases

Custos

Professor Tuula Salo, University of Oulu, Faculty of Medicine, Cancer and Translational Medicine Research Unit

Factors affecting aggressive oral tongue cancer invasion and development of in vitro models for chemoradiotherapy assay

Oral tongue squamous cell carcinoma (OTSCC) is the most prevalent cancer of the oral cavity. The tumor microenvironment (TME) involves the extracellular matrix and the surrounding non-cancerous cells as well as a variety of signal molecules. We studied the effect of proteolytic enzymes and inflammatory cells associated with TME in the invasion of tongue carcinoma cells. In addition, we evaluated the feasibility of our human myoma tissue -based invasion models for chemoradiotherapy assay.

Myoma tissue mimics the TME of solid human tumors, and it contains a variety of non-vital cells and soluble invasion related factors. Therefore, myoma-based invasion models offer a more realistic environment for invasion assays conducted with human carcinoma cells, compared to models based on animal tissue . In this study we showed that our human uterine leiomyoma-based invasion models, myoma discs and Myogel, are reliable methods for testing the effects of chemoradiation treatment on human carcinoma cells.

Tumor associated macrophages (TAM) induce the progression of cancer tumor and TAMs are associated with poor prognosis in different cancer types. The presence of TAM-like M2 macrophages induced migration and invasion of OTSCC cells. Furthermore, the level of signal molecules associated with oral cancer progression were increased when OTSCC cells were co-cultured with M2 macrophages. These results indicate that macrophages, especially TAMs, are actively involved in the progression of OTSCC, thus they could be potential target cells in OTSCC treatments.

Heparanases are enzymes capable of degrading heparin sulphate which is a crucial component of the extracellular matrix. We found that blocking of heparanase activity in combination with therapeutic doses of irradiation may induce cell invasion of oral tongue squamous cell carcinoma cells.

Matrix metalloproteinases are proteolytic enzymes also capable of degrading the structural components of extracellular matrix. To elucidate the role of MMP9 in OTSCC progression, we used various models where production or activity of MMP9 was altered. We found that the increased MMP9 expression in the highly malignant OTSCC cell line HSC-3 leads to reduced motility, but increased proliferation of the cells. This could give rise to an increased tumor growth, but less invasive behavior.

Dissertation

Last updated: 5.6.2019