Starts in a primary tumour
Progression of the primary tumour, invasion of the surrounding tissue and the ability to form distant metastases depends on a series of sequential events. The metastatic process starts in a primary tumour. Upon progression of most primary tumours, the tumour cells undergo a decrease in their adhesive properties and an increase in their motility.
However, not only is it the specific properties of the tumour cells themselves, but also those of the surrounding environment that are important for tumour metastasis. Interference with any of these events can delay or prevent metastatic disease.
Focus on Wnt-5a signalling
The present programs focus on the role of the Wnt-5a protein in the metastatic process. The Wnt proteins belong to a family of secreted glycoproteins that participate in tumourigenesis via an autocrine or paracrine route. Secreted Wnt proteins bind to and activate G-protein-coupled receptors of the Frizzled (Fzd) family.
In addition, there are co-receptors to the Fzd receptors that influence the Wnt-induced signalling.
First report on Wnt-5a protein levels in clinical cancer material
Dr. Andersson’s research group published the first report on how the protein expression level of Wnt-5a in cancer cells correlates with the outcome of the disease, and this data revealed that low-level expression of Wnt-5a protein in primary invasive breast carcinomas is associated with higher histological grade (poor differentiation) and shortened recurrence-free survival.
These findings were further confirmed with regard to disease-related death in a different breast cancer cohort. Increased proliferation was not the reason for the increased metastatic activity in these patients, but more likely it was due to an increased motile behaviour of the tumour cells. A similar role for Wnt-5a as tumour suppressor has been described in thyroid-, prostate-, colorectal cancer and in some hematological malignancies.