Micro-Raman detection of nuclear membrane lipid fluctuations in senescent epithelial breast cancer cells.

ABSTRACT

Originally identified in cultured cells, oncogenic cellular senescence is a growth-arrest mechanism which may inhibit tumor development by limiting the ability of cells to divide. However, literature shows that these cells secrete tumor-inducing and tumor-suppressing proteins leading to poor prognosis. Understanding the progression of oncogenic cellular senescence and associated mechanisms provides important implications for improving tumorigenesis therapeutic treatments. Micro-Raman spectroscopic imaging has grown in popularity as an imaging technique compared to the standard imaging predecessors and can be attributed to its numerous benefits such as no sample perturbation and the provision of direct chemical information. Through the use of label-free micro-Raman spectroscopy, control and senescent cells were noninvasively imaged. Resulting spectral images were processed using chemometric techniques, and average nuclei spectra from each sample set were compared. In turn, changes in the -cis and -trans unsaturated lipid isomer content were found to differ among proliferating and senescent cells. This may lead to increased nuclear fluidity and may contribute to the inability of senescent cells to complete the cell cycle. In the tumor environment, this detected increase in nuclear envelope fluidity could lead to downstream gene expression modifications and increased nucleo-cytoplasmic RNA translocation. Understanding nuclear envelope fluidity could provide insight into secretory profiles of senescent cells and their role in carcinogenesis, meriting further investigation into novel therapeutic technique development for oncogenic cellular senescence.