Most cancer-related deaths during the malginant cancer progression are caused by the ability of cancer cells to metastasize. The process of metastasis follows a linear propagation of several steps. It starts with the spreading of cancer cells from the primary tumor, which then migrate into the local tumor microenvironment. The cancer cells can transmigrate into blood or lymph vessels (intravasation), get transported through the vessel flow, adhere to the endothelial cell lining, grow and form a secondary tumor directly inside the vessel or the cancer cells possibly transmigrate through the endothelial vessel lining (extravasation) into the extracellular matrix of connective tissue. After this step, the cancer cells migrate further into the targeted tissue (possibly another organ), grow and form a secondary tumor (i.e. the tumor metastasizes).


Despite of all current findings based on biochemistry and even the novel approaches based on genomics and proteomics cancer research did not fundamentally change cancer death rates, but still improved clinical diagnosis substantially in the field of cancer research regarding the classification and detailed staging of tumors, numerous marker proteins and mapping of specific human cancer-types. Thus, a main criticism to these methods is that the expression levels of numerous genes and molecules, which are differently regulated during cancer progression, depend on the cancer disease stage. In particular, it is still not fully understood how they regulate cancer progression. A reason may be that these genomic and proteomic based methods do not account for the localization of the molecules in special compartments such as lipid rafts, their activation or assembly state, their life-time, turn-over-, modification- and recycling rate.


Thus, we and others propose that the biomechanical properties are crucial for the efficiency and speed of cancer cell invasion and subsequently, for metastases formation. In more detail, classical physical approaches will be adopted to complex soft matter such as cancer cells and novel biophysical methods will be developed in order to adopt them to cancer research. These novel physical approaches have so far changed or will still alter the direction of recent cancer research.


Moreover, even the role of the endothelium during the transmigration and invasion of cells is not clear, it has been seen as passive barrier, but this could not explain all novel findings as our finding that this endothelial layer of vessels can enhance the invasiveness of cancer cells. Thus, we will investigate how cancer cells alter the structural, biochemical and mechanical properties of the endothelium to regulate their own invasiveness through extracellular matrices and hence, through the tissue microenvironment. Moreover, we will investigate how the mechanical properties of cancer cells regulate the functional properties such as cancer cell invasion and transendothelial migration.


Finally, our research will shed light on the mechanical properties of cancer cells and the interacting endothelium and will point out the importance of the mechanical properties as a critical determinant for the efficiency of cancer cell invasion and the overall progression of cancer. In conclusion, we suggest that the regulation of the endothelial cells biomechanical properties by cancer cells and the mechanical properties of cancer cells are a critical determinants of cancer cell invasiveness and may affect the future development of new cancer treatments.

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