Abstract
Cancer cells are known to secrete many bioactive factors acting both with paracrine and autocrine mechanisms by which they condition the surrounding microenvironment. At the same time, the intracytoplasmic metabolic activities microenvironment influences the profile of this secretion. It is well known that cancer cells exhibit prevalent glycolytic metabolism and a more oxidative atmosphere compared to their healthy counterparts; this metabolic phenotype promotes glycate adducts formation and secretion. Considering the exacerbation of metabolic changes during the cancer progression, it is suggestive to explore the potential correlation between the increasing rate of glycan adducts and the specific pattern of secreted cytokines in different phases of cancer disease. We analyzed the secretomes of blood-derived cancer cell cultures from cancer patients and healthy subjects. The relative glycate adducts content in cancer secretomes was higher in comparison to that of healthy samples. Moreover, the stratification based on different phases of cancer disease correlated with a specific cytokines panel. The results obtained open a new perspective of observation of the intricate relationship between metabolome and inflammation in cancer. By using the analysis of secretome combined with a standardized protocol of liquid biopsy, it would be possible to identify specific profiles of molecular markers useful to arrange alternative and personalized medicine strategies.
Highlights
The isolation of cancer cells for their profiling has always been a challenge, especially in the advanced stages of the disease
Over the last few years, circulating tumour cells have become the subject of researches for their great potential in indicating cancer occurrence, and in providing fundamental information about the physiology of cancer cells
Much progress has currently been made in the study of circulating nucleic acids from tumour cells, but coupling appropriate therapies to the effects of genetic mutations is currently limited by an incomplete understanding of the interplay between the tumour cell and its microenvironment
Summary
The isolation of cancer cells for their profiling has always been a challenge, especially in the advanced stages of the disease. We overcame the stumbling block of the rare population by exploiting their intrinsic prerogative to proliferate The analysis of their secretome provides direct information about the amount and type of secreted molecules by cultured cells (14) and possibly on the activated metabolic pathways, as previously reported (12–14). We analyzed and correlated the content of adducts of methylglyoxal referencing the oxidative stress and secreted cytokines as an inflammation reference in the secretome obtained from blood-derived cultures. It is well known from the early past century that cancer cells switch their metabolic profile enhancing the glucose uptake so, today this characteristic is exploited in cancer imaging. We tried to dissect the relationship between glycation adducts richness, which is the expression of metabolic switch, and the specific pattern of secreted cytokines inside their own secretome, with the prospect of understanding how this molecular signature could influence the tumour microenvironment, the diagnostic and prognostic contexts
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