TOF-SIMS imaging reveals tumor heterogeneity and inflammatory response markers in the microenvironment of basal cell carcinoma

Nilsson, Kelly Dimovska; Neittaanmäki, Noora; Zaar, Oscar; Angerer, Tina B.; Paoli, John; Fletcher, John S.

doi:10.1116/6.0000340

Cited by 22 publications

(15 citation statements)

References 38 publications

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“…For this reason, an increasing number of MSI devices offer high-resolution mass analyzers and tandem-MS capability for structural identification to enhance specificity . With these capabilities, MSI has significantly contributed to the field of lipidomics by revealing lipid alterations in various diseases. − …”

Section: Introductionmentioning

confidence: 99%

Evaluation of 6 MALDI-Matrices for 10 μm Lipid Imaging and On-Tissue MSn with AP-MALDI-Orbitrap

Angerer

Bour

Biagi

et al. 2022

J. Am. Soc. Mass Spectrom.

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Mass spectrometry imaging is a technique uniquely suited to localize and identify lipids in a tissue sample. Using an atmospheric pressure (AP-) matrix-assisted laser desorption ionization (MALDI) source coupled to an Orbitrap Elite, numerous lipid locations and structures can be determined in high mass resolution spectra and at cellular spatial resolution, but careful sample preparation is necessary. We tested 11 protocols on serial brain sections for the commonly used MALDI matrices CHCA, norharmane, DHB, DHAP, THAP, and DAN in combination with tissue washing and matrix additives to determine the lipid coverage, signal intensity, and spatial resolution achievable with AP-MALDI. In positive-ion mode, the most lipids could be detected with CHCA and THAP, while THAP and DAN without additional treatment offered the best signal intensities. In negative-ion mode, DAN showed the best lipid coverage and DHAP performed superiorly for gangliosides. DHB produced intense cholesterol signals in the white matter. One hundred fifty-five lipids were assigned in positive-ion mode (THAP) and 137 in negative-ion mode (DAN), and 76 peaks were identified using on-tissue tandem-MS. The spatial resolution achievable with DAN was 10 μm, confirmed with on tissue line-scans. This enabled the association of lipid species to single neurons in AP-MALDI images. The results show that the performance of AP-MALDI is comparable to vacuum MALDI techniques for lipid imaging.

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Section: Introductionmentioning

confidence: 99%

Evaluation of 6 MALDI-Matrices for 10 μm Lipid Imaging and On-Tissue MSn with AP-MALDI-Orbitrap

Angerer

Bour

Biagi

et al. 2022

J. Am. Soc. Mass Spectrom.

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“…On the other hand, PCs, which carry two chains of FA, presented a predominance of chains from 16 to 20 carbons, with the SFAs predominant over MUFAs and PUFAs. This could be indicative that chronic inflammation is characterized by an increase in even SFAs between 16 and 18 carbons [ 50 , 51 , 52 ]. This observation suggests that chronic inflammation could induce long-term changes in the metabolism of SFAs through increasing their circulation bound to phospholipids [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Imbalances in TCA, Short Fatty Acids and One-Carbon Metabolisms as Important Features of Homeostatic Disruption Evidenced by a Multi-Omics Integrative Approach of LPS-Induced Chronic Inflammation in Male Wistar Rats

Hernandez-Baixauli

Abasolo

Palacios

et al. 2022

IJMS

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Chronic inflammation is an important risk factor in a broad variety of physical and mental disorders leading to highly prevalent non-communicable diseases (NCDs). However, there is a need for a deeper understanding of this condition and its progression to the disease state. For this reason, it is important to define metabolic pathways and complementary biomarkers associated with homeostatic disruption in chronic inflammation. To achieve that, male Wistar rats were subjected to intraperitoneal and intermittent injections with saline solution or increasing lipopolysaccharide (LPS) concentrations (0.5, 5 and 7.5 mg/kg) thrice a week for 31 days. Biochemical and inflammatory parameters were measured at the end of the study. To assess the omics profile, GC-qTOF and UHPLC-qTOF were performed to evaluate plasma metabolome; 1H-NMR was used to evaluate urine metabolome; additionally, shotgun metagenomics sequencing was carried out to characterize the cecum microbiome. The chronicity of inflammation in the study was evaluated by the monitoring of monocyte chemoattractant protein-1 (MCP-1) during the different weeks of the experimental process. At the end of the study, together with the increased levels of MCP-1, levels of interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α) and prostaglandin E2 (PGE2) along with 8-isoprostanes (an indicative of oxidative stress) were significantly increased (p-value < 0.05). The leading features implicated in the current model were tricarboxylic acid (TCA) cycle intermediates (i.e., alpha-ketoglutarate, aconitic acid, malic acid, fumaric acid and succinic acid); lipids such as specific cholesterol esters (ChoEs), lysophospholipids (LPCs) and phosphatidylcholines (PCs); and glycine, as well as N, N-dimethylglycine, which are related to one-carbon (1C) metabolism. These metabolites point towards mitochondrial metabolism through TCA cycle, β-oxidation of fatty acids and 1C metabolism as interconnected pathways that could reveal the metabolic effects of chronic inflammation induced by LPS administration. These results provide deeper knowledge concerning the impact of chronic inflammation on the disruption of metabolic homeostasis.

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“…Thus, depending on the histopathological type, BCC can be considered a more aggressive or less aggressive tumor. However, in many cases, areas with aggressive growth patterns and areas with a less aggressive pattern have been present in BCC samples [ 203 ].…”

Section: The Role Of Mmps In Bcc Pathogenesismentioning

confidence: 99%

Current Perspectives on the Role of Matrix Metalloproteinases in the Pathogenesis of Basal Cell Carcinoma

et al. 2021

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Basal cell carcinoma (BCC) is the most common skin malignancy, which rarely metastasizes but has a great ability to infiltrate and invade the surrounding tissues. One of the molecular players involved in the metastatic process are matrix metalloproteinases (MMPs). MMPs are enzymes that can degrade various components of the extracellular matrix. In the skin, the expression of MMPs is increased in response to various stimuli, including ultraviolet (UV) radiation, one of the main factors involved in the development of BCC. By modulating various processes that are linked to tumor growth, such as invasion and angiogenesis, MMPs have been associated with UV-related carcinogenesis. The sources of MMPs are multiple, as they can be released by both neoplastic and tumor microenvironment cells. Inhibiting the action of MMPs could be a useful therapeutic option in BCC management. In this review that reunites the latest advances in this domain, we discuss the role of MMPs in the pathogenesis and evolution of BCC, as molecules involved in tumor aggressiveness and risk of recurrence, in order to offer a fresh and updated perspective on this field.

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TOF-SIMS imaging reveals tumor heterogeneity and inflammatory response markers in the microenvironment of basal cell carcinoma

Cited by 22 publications

References 38 publications

Evaluation of 6 MALDI-Matrices for 10 μm Lipid Imaging and On-Tissue MSn with AP-MALDI-Orbitrap

Evaluation of 6 MALDI-Matrices for 10 μm Lipid Imaging and On-Tissue MSn with AP-MALDI-Orbitrap

Imbalances in TCA, Short Fatty Acids and One-Carbon Metabolisms as Important Features of Homeostatic Disruption Evidenced by a Multi-Omics Integrative Approach of LPS-Induced Chronic Inflammation in Male Wistar Rats

Current Perspectives on the Role of Matrix Metalloproteinases in the Pathogenesis of Basal Cell Carcinoma

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