Cancer metabolic features allow discrimination of tumor from white blood cells by label-free multimodal optical imaging

Abstract

Circulating tumor cells (CTCs) are tumor cells that have penetrated the circulatory system preserving tumor properties and heterogeneity. Detection and characterization of CTCs has high potential clinical values and many technologies have been developed for CTC identification. These approaches remain challenged by the extraordinary rarity of CTCs and the difficulty of efficiently distinguishing cancer from the much larger number of white blood cells in the bloodstream. Consequently, there is still a need for efficient and rapid methods to capture the broad spectrum of tumor cells circulating in the blood. Herein, we exploit the peculiarities of cancer metabolism for discriminating cancer from WBCs. Using deuterated glucose and Raman microscopy we show that a) the known ability of cancer cells to take up glucose at greatly increased rates compared to non-cancer cells results in the lipid generation and accumulation into lipid droplets and, b) by contrast, leukocytes do not appear to generate visible LDs. The difference in LD abundance is such that it provides a reliable parameter for distinguishing cancer from blood cells. For LD sensitive detections in a cell at rates suitable for screening purposes, we test a polarization-sensitive digital holographic imaging (PSDHI) technique that detects the birefringent properties of the LDs. By using polarization-sensitive digital holographic imaging, cancer cells (prostate cancer, PC3 and hepatocarcinoma cells, HepG2) can be rapidly discriminated from leukocytes with reliability close to 100%. The combined Raman and PSDHI microscopy platform lays the foundations for the future development of a new label-free, simple and universally applicable cancer cells’ isolation method.

Application of Raman spectroscopy to the evaluation of F-actin changes in sea urchin eggs at fertilization

“…no need for microinjection of fluorescent markers). As such, Raman spectroscopy provides highly chemical-specific information on the sample, which can be interpreted for diagnostic purposes, as evidenced by previous work on cancer cell/tissue identification (Managó et al, 2016;Elumalai et al, 2020;Liu et al, 2022;Mangini et al, 2023). When a morphological change occurs in a selected cell or tissue during a biological process such as cell division, apoptosis, or stress response, this change can be identified, quantified, and visualized thanks to the consequent variation of the Raman spectrum (Short et al, 2005;Brauchle et al, 2014).…”

Noninvasive discrimination of prostate healthy and cancer cells by quantitative phase and Raman imaging

“…DHM generates quantitative morphological data on cells, including volume and surface area, without the need for labels. Recent advancements in polarization-sensitive DHM (PSDHM) allow for the measurement of birefringence, a property sensitive to the polarization-dependent refractive index of cellular components 4 . This technique holds particular promise for detecting lipid droplets (LDs), which are abundant in cancer cells and exhibit high birefringence due to the presence of cholesteryl esters 5 .…”

AI-aided holographic flow cytometry for label-free identification of ovarian cancer cells in the presence of unbalanced datasets

“…Commonly used indicators are cancer-specific surface antigens; however, given the high tumoral heterogeneity, antigen-based methods often lead to false negative results. To overcome biased epitope analyses, methods based on the recognition of peculiar functional CTC properties are being developed, such as matrigel invasion capacity 11 or high glycolytic metabolism, 12 which to date, do not offer the high-throughput levels required for screening programs. On the other hand, using next-generation sequencing (NGS) analysis to identify tumor-specific mutations in the bloodstream offers greater potential in terms of throughput, but often depends on cumbersome CTC enrichment steps and requires cell destruction.…”