Background
Malignant rhabdoid tumours (MRT) are the rarest yet aggressive malignancies in children under three years old(1). MRTs commonly occur renally and some extrarenally including in lungs and liver. The key genetic aberration identified in MRTs is the complete loss of SMARCB1 gene, a tumour suppressor, which encodes a core subunit of the SWitch/Sucrose Non-Fermentable (SWI/SNF) complex(2). Although the tumour suppressive role of SMARCB1 is investigated, SMARCB1’s role in tumour metastasis when not expressed is yet to be determined(3). This study is centred on that knowledge gap and investigates the correlation between MRT metastasis and the SMARCB1 gene expression.
Methods
SMARCB1 inducible cell lines (F22, STMpc), control MRT (G-401, STM91-01) and human embryonic kidney and lung cell lines (HEK-293, HLF1) were explored. Firstly, the expression variability of the other subunits of SWI/SNF complex was determined with and without the expression of SMARCB1 by qPCR analysis. Secondly, some metastatic and invasive markers were observed for their regulation with or without SMARCB1 gene by qPCR analysis. Cell viability and metabolism were also noted along with cell migratory properties using scratch wound and transwell migration assays.
Results
Significant variability of thirteen subunits of the SWI/SNF complex was identified in cell lines with and without the SMARCB1 gene expression. Cell viability and metabolism have shown a significant decrease in uninduced SMARCB1 cell lines compared to the induced. Furthermore, cell migration was also increased in uninduced SMARCB1 cell lines similar to cell invasion. Chosen metastatic and invasive markers are variably regulated in cell lines without the SMARCB1 gene.
Conclusion
It is evident from the results that SMARCB1 loss induces metastatic characteristics in kidney and lung cells. To further understand the metastatic properties of the SMARCB1 loss, the inducible cell lines will be injected into a zebrafish model to assess the expression of metastatic markers.