Cancer invasion and subsequent formation of distant metastasis is a major clinical issue. Invasive cells have somehow lost their contacts with the neighbouring cells and adopted abnormal migratory properties that enable their invasion into the surrounding tissues. In normal epithelia, mechanosensitive actomyosin structures play a major role in the maintenance of cell-cell junctions through production of cell-mediated forces. However, during neoplastic progression, their regulation may be altered, subsequentally leading to abnormal cell-exerted forces, disruption of the epithelial integrity as well as to abnormal migratory properties of the cells. In our studies we aim in understanding the early events in cancer cell dissamination: How does altered regulation of mechanosensitive actomyosin bundles lead to scattering of cancer cells? What is the role of tumor stroma in this process? And how do cancer cells utilize abnormal cellular forces in invasion to the surroundings? In our research we focus on breast cancer but the mechanisms behind the early events, preceeding invasive stage, may be common for other types of solid tumors as well.
model systems and methodology
In our studies we utilize both human and canine mammary epithelial cell lines, and a variety of molecular –and cell biological methods, proteomics, as well as advanced imaging methods. In addition to established cell lines, we utilize primary samples isolated from either normal or transformed canine mammary glands. Canine mammary tumors (CMTs) provide an excellent natural model for the heterogeneous group of human breast carcinomas. Compared to human, CMTs have histopathologically similar cancer subtypes as well as pre-neoplasias and share the same risk factors for the onset of this disease. Additionally, the expression of several lineage-specific markers in basal and luminal cell populations is identical in canine and human. Canine mammary material is received from the patients of Helsinki University Small Animal Hospital after tumor removal. This patient material is undergoing histopathological examination and specific cell types are also isolated for further studies in cell culture to understand the tumor-stroma interplay.
In the Image: example of monolayer traction force map of MDCK cells