Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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Gewählte Publikation:

Zacharias, M.
Regulation of tumor cell migration in non-small cell lung cancer
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2017. pp. 91 [OPEN ACCESS]


Autor*innen der Med Uni Graz:
Zacharias Martin
Brcic Luka
Dandachi Nadia

Due to the nonmotile nature of adult epithelia, carcinomas are considered to undergo an epithelial-to-mesenchymal transition (EMT) before they start to migrate. However, histopathological findings provide evidence for an alternative mode of tumor cell migration beyond classical EMT: Instead of migrating as separated single cells, which would be the logical consequence of a complete EMT-program, carcinomas often move in multicellular complexes. Despite these facts, relatively little is known about the actual mechanisms behind the movement of tumor cell bulks. Therefore, we aimed to further examine bulk cell migration in non-small cell lung cancer (NSCLC) patient samples using immunohistochemistry. As a first step, 30 surgically resected NSCLC specimens were immunohistochemically evaluated in terms of expression and distribution of EMT-markers and molecules associated with migration and metastasis in general. The selected cases were all characterized by vascular invasion. Consequently, the expression of the respective markers was compared between the primary tumor, the invasion front, and the vascular invasion site. Finally, to validate our findings in a larger cohort and to avoid a selection bias, tissue microarrays with 528 NSCLC cases were additionally evaluated for selected markers of interest. Twist was the only EMT transcription factor which was expressed in all cases of the study set. However, TGFß, a molecule known to upregulate Twist and induce EMT, was negative in all cases. Snail was only minimally expressed in less than half of our cases. The fact that ZEB1 and Slug were both negative in almost all tumors, provides further evidence for an incomplete EMT. The coexpression of E-cadherin and N-cadherin in all 30 cases indicates a cell phenotype that is not exclusively mesenchymal or epithelial, but rather a state in between. The markers pERK, RhoA, FAK, ILK, and YAP1 were downregulated at the invasive sites compared to the tumor center. Conversely, the markers Vimentin, Mad, Brk, Rab40B, Tks5, Fascin, and PLC¿ were clearly upregulated at the invasive sites. In conclusion, presented data provide evidence of significant differences in the expression of involved molecules between single cell and collective cell invasion, including the presence of a partial EMT rather than EMT in its classical binary form.

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