Research: 2018 – Manitoba (Mai)

Project Title:
Lamin A/C levels in circulating tumor cells
Investigators:
Sabine Mai, University of Manitoba
Project Abstract:
Lamin A/C is a protein present in all cells. Among its many functions, it also contributes to the normal organization of the cell’s nucleus. It helps anchor the DNA and keeps it in the correct place within the 3D space of the nucleus. The absence of lamin A/C leads to changes in the organization of the nucleus, including changes in positions of the genetic material in the nucleus, slower cell growth, early onset of ageing and early cell death. Lamin A/C was described as one factor that is upregulated in prostate cancer when the cancer becomes aggressive and forms metastatis. However, no knowledge exists about lamin A/C in circulating tumor cells (CTCs) and in relation to disease aggressiveness that may be predictable using CTCs and liquid biopsies (instead of
tissue biopsies). We have previously characterized the stability or aggressive behaviour of prostate cancer CTCs using 3D imaging of telomeres. Our data suggest a very good stratification of patients into stable or aggressive. We hypothesize that lamin A/C may make this classification even more accurate and propose to test it in parallel with 3D telomere profiling in CTCs of prostate cancer patients of low, intermediate and high risk.
Scientific Abstract:
Three-dimensional (3D) nuclear telomere analysis of circulating tumor cells (CTCs), a technology developed by our group, allowed us to stratify patients with the identical Gleason 7 grading of intermediate risk prostate cancer into three subgroups. The three new subgroups differed in their risk to disease progression from low (20% risk), to intermediate (50% risk) and high risk (68.75% risk). In the proposed study, we will add a second marker to this analysis, namely the measurement of lamin A/C in CTCs. This work has never been done on CTCs, but our lab has experience in performing this staining in other cancers. We expect no problems in the use of the
method and expect the risk assessment of individual patients to get even better when this marker is added.
Impact on prostate cancer patients:
It contributes to more precise risk stratification of patients with aggressive/progressive disease.