Laboratory of Cancer Cell Invasion
The laboratory of cancer cell invasion is investigating molecular and morphological processes required for successful invasion of cancer cells and molecular aspects of cell transformation.
The spread of cancer from its tissue of origin and its subsequent growth in other organs is the most life threatening aspect of the disease. This process is called metastasis, and is comprised of a series of critical steps known as the metastatic cascade. The cascade involves the invasion of cells from the primary tumor into the surrounding tissue, intravasation and transport in the blood or lymphatic system, extravasation, and proliferation of tumor cells at the secondary sites. The most critical step of metastasis is invasion. Three main modes of overcoming the barrier of the surrounding tissue by tumor cells were described: the mesenchymal, collective and amoeboid mode. The mesenchymal and collective modes of invasion are both characterized by proteolytic depend remodeling of surrounding tissue and integrin mediated cell tissue contacts. Amoeboid invasion is proteolysis and integrin independent and characterized by increased activity of the Rho kinase ROCK. In addition we have strong interest in analysis of the role of integrin-mediated signaling in mesenchymal invasiveness.
During its short existence our laboratory has accomplished already some important achievements. Our group discovered amoeboid invasiveness as a primary mode of invasion in cancer cells of mesenchymal type (sarcoma) and at the same time we directly correlated up- regulation of Rho/ROCK signaling in amoeboid invasiveness with greater capability to generate protrusive force at the leading edge (Rösel et al., 2008). We were first to describe the morphology of invadopodia in a complex 3D environment. We have shown that invadopodia in 3D has a very different morphology when compared to that observed on flat 2D surfaces. Invadopodia in 3D consist of concave base, from which a number of thin filopodia-like protrusions extend into the ECM (Tolde et al., 2010). We also proved the existence of focal adhesions in a complex 3D environment and showed they are of comparable size and dynamics as focal adhesions in 2D (Tolde et al., 2010). Recently, we have proved the role of CAS SH3 domain tyrosine phosphorylation in migration and invasiveness of Src- transformed cells (Janostiak et al., 2011). Currently we analyze the role of tyrosine phosphorylation within SH3 domains as a possible novel general regulatory mechanism of cell signaling (Tatárová et al., 2012).
Daniel Rösel (Ph.D.)
Lenka Koudelková (Mgr.)
Lab location: BIOCEV (Vestec, Průmyslová); room A2.103, +420 325873902, e-mail: firstname.lastname@example.org
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