Abstract:Colorectal cancer (CRC) is the fourth leading cause of cancer death in the world. Despite the screening programs, its incidence in the population below the 50s is increasing. Therefore, new stratification protocols based on multiparametric approaches are highly needed. In this scenario, the lipidome is emerging as a powerful tool to classify tumors, including CRC, wherein it has proven to be highly sensitive to cell malignization. Hence, the possibility to describe the lipidome at the level of lipid species ha… Show more
“…In addition, we observed a clear tendency in phosphatidylinositol (PI) decreasing in AD, Neo, and Her patients compared to healthy ones (14.9%, 10.5%, and 11.8%, respectively). These results are in line with the literature [48] and in agreement with our previous study in CRC cell lines [43].…”
Section: Isolated Ev Membrane Lipidome Shows Changes In Phosphatidylcholine Content In Compromised Patientssupporting
confidence: 94%
“…The analysis of commercial cell line-derived EVs showed that the lipid composition of these vesicles is very sensitive to their origin [ 43 ]. Thus, we sought to establish whether this discriminatory potential would persist in a more complex biological matrix and context: plasma and patients.…”
Section: Resultsmentioning
confidence: 99%
“…In fact, there is a growing interest in establishing EV lipid composition as evidence that lipids play specific roles in EV physiology [ 68 ]. Taking into account all this evidence, together with our previous results showing that the EV lipidome do retain certain features at the compositional level of the cell origin [ 43 ], we explored the feasibility of plasma-derived EV lipidome to identify clinical biomarkers in patients at different stages of CRC.…”
Section: Discussionmentioning
confidence: 99%
“…In previous studies, we characterized the membrane lipidome of five commercial colon cell lines and their extracellular vesicles, demonstrating that both cell and EV lipidome was able to classify cells according to their malignancy [ 43 ]. These results prompted us to investigate the use of the lipidome of EVs derived from biological fluids as a source of non-invasive biomarkers for cancer.…”
Even though colorectal cancer (CRC) is one of the most preventable cancers, it is currently one of the deadliest. Worryingly, incidence in people <50 years has increased unexpectedly, and for unknown causes, despite the successful implementation of screening programs in the population aged >50 years. Thus, there is a need to improve early diagnosis detection strategies by identifying more precise biomarkers. In this scenario, the analysis of exosomes is given considerable attention. Previously, we demonstrated the exosome lipidome was able to classify CRC cell lines according to their malignancy. Herein, we investigated the use of the lipidome of plasma extracellular vesicles as a potential source of non-invasive biomarkers for CRC. A plasma exosome-enriched fraction was analyzed from patients undergoing colonoscopic procedure. Patients were divided into a healthy group and four pathological groups (patients with hyperplastic polyps; adenomatous polyps; invasive neoplasia (CRC patients); or hereditary non-polyposis CRC. The results showed a shift from 34:1- to 38:4-containing species in the pathological groups. We demonstrate that the ratio Σ34:1-containing species/Σ38:4-containing species has the potential to discriminate between healthy and pathological patients. Altogether, the results reinforce the utility of plasma exosome lipid fingerprint to provide new non-invasive biomarkers in a clinical context.
“…In addition, we observed a clear tendency in phosphatidylinositol (PI) decreasing in AD, Neo, and Her patients compared to healthy ones (14.9%, 10.5%, and 11.8%, respectively). These results are in line with the literature [48] and in agreement with our previous study in CRC cell lines [43].…”
Section: Isolated Ev Membrane Lipidome Shows Changes In Phosphatidylcholine Content In Compromised Patientssupporting
confidence: 94%
“…The analysis of commercial cell line-derived EVs showed that the lipid composition of these vesicles is very sensitive to their origin [ 43 ]. Thus, we sought to establish whether this discriminatory potential would persist in a more complex biological matrix and context: plasma and patients.…”
Section: Resultsmentioning
confidence: 99%
“…In fact, there is a growing interest in establishing EV lipid composition as evidence that lipids play specific roles in EV physiology [ 68 ]. Taking into account all this evidence, together with our previous results showing that the EV lipidome do retain certain features at the compositional level of the cell origin [ 43 ], we explored the feasibility of plasma-derived EV lipidome to identify clinical biomarkers in patients at different stages of CRC.…”
Section: Discussionmentioning
confidence: 99%
“…In previous studies, we characterized the membrane lipidome of five commercial colon cell lines and their extracellular vesicles, demonstrating that both cell and EV lipidome was able to classify cells according to their malignancy [ 43 ]. These results prompted us to investigate the use of the lipidome of EVs derived from biological fluids as a source of non-invasive biomarkers for cancer.…”
Even though colorectal cancer (CRC) is one of the most preventable cancers, it is currently one of the deadliest. Worryingly, incidence in people <50 years has increased unexpectedly, and for unknown causes, despite the successful implementation of screening programs in the population aged >50 years. Thus, there is a need to improve early diagnosis detection strategies by identifying more precise biomarkers. In this scenario, the analysis of exosomes is given considerable attention. Previously, we demonstrated the exosome lipidome was able to classify CRC cell lines according to their malignancy. Herein, we investigated the use of the lipidome of plasma extracellular vesicles as a potential source of non-invasive biomarkers for CRC. A plasma exosome-enriched fraction was analyzed from patients undergoing colonoscopic procedure. Patients were divided into a healthy group and four pathological groups (patients with hyperplastic polyps; adenomatous polyps; invasive neoplasia (CRC patients); or hereditary non-polyposis CRC. The results showed a shift from 34:1- to 38:4-containing species in the pathological groups. We demonstrate that the ratio Σ34:1-containing species/Σ38:4-containing species has the potential to discriminate between healthy and pathological patients. Altogether, the results reinforce the utility of plasma exosome lipid fingerprint to provide new non-invasive biomarkers in a clinical context.
“…The intensity of lipid species eliciting opposing trends in the experimental groups is exemplified by the ethyl ethers PC O-16:0/16:0 and PC O-16:0/18:1, which are expressed more strongly in malignant cells ( Figure S2A ), and by SM d18:1/16:0 and PE P-18:0/22:4, that were particularly abundant in melanocytes ( Figure S2B ). Figure S2 also provides clear examples of the heterogeneity in lipid expression across the cell lines analyzed, which were used to model a condition, as also seen for colon cancer cell lines [ 33 ].…”
Melanoma is the deadliest form of skin cancer due to its ability to colonize distant sites and initiate metastasis. Although these processes largely depend on the lipid-based cell membrane scaffold, our understanding of the melanoma lipid phenotype lags behind most other aspects of this tumor cell. Here, we examined a panel of normal human epidermal and nevus melanocytes and primary and metastatic melanoma cell lines to determine whether distinctive cell-intrinsic lipidomes can discern non-neoplastic from neoplastic melanocytes and define their metastatic potential. Lipidome profiles were obtained by UHPLC-ESI mass-spectrometry, and differences in the signatures were analyzed by multivariate statistical analyses. Significant and highly specific changes in more than 30 lipid species were annotated in the initiation of melanoma, whereas less numerous changes were associated with melanoma progression and the non-malignant transformation of nevus melanocytes. Notably, the “malignancy lipid signature” features marked drops in pivotal membrane lipids, like sphingomyelins, and aberrant elevation of ether-type lipids and phosphatidylglycerol and phosphatidylinositol variants, suggesting a previously undefined remodeling of sphingolipid and glycerophospholipid metabolism. Besides broadening the molecular definition of this neoplasm, the different lipid profiles identified may help improve the clinical diagnosis/prognosis and facilitate therapeutic interventions for cutaneous melanoma.
Current cancer treatments damage healthy cells and tissues, causing short‐term and long‐term side effects. New treatments are desired that show greater selectivity toward cancer cells and evade the common mechanisms of multidrug resistance. Membranolytic anticancer peptides (mACPs) hold promise against cancer and multidrug resistance. Amphipathicity, hydrophobicity, and net charge of mACPs participate in their respective interactions with cell membranes and their overall inhibition of cancer cells. To support the design of cell‐line selective mACPs, we investigated the relationships that amino acid composition, physicochemical properties, sequence motifs, and sequence homology could have with their potency and selectivity towards several healthy and cancer cell lines. Sequence length and net charge are known to affect the selectivity of mACPs between cancer and healthy cell lines. Our study reveals that increasing the net charge or flexibility (i. e., small and aliphatic residues) influences their selectivity between cancer cell lines with comparable lipid compositions.
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