Proline Metabolism in Cell Regulation and Cancer Biology: Recent Advances and Hypotheses

Phang, James M.

doi:10.1089/ars.2017.7350

Cited by 202 publications

(213 citation statements)

References 105 publications

(223 reference statements)

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“…Thus, when cells are proliferating or not, they can store or not their metabolic substrates in the ECM 26,29 . However, when collagen is degrading, Proline is converted in amino acids 42 . This process is what has been highlighted by the RS, with bands assigned to Proline and collagen progressively less intense from EC to CS G1 and Cs G2, and the intensification of bands assigned to Tyr and Trp, as well as to the Phe for the CS G3.…”

Section: Discussionmentioning

confidence: 99%

Contribution of Raman Spectroscopy to Diagnosis and Grading of Chondrogenic Tumors

D’Acunto

Gaeta

Capanna

et al. 2020

Sci Rep

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In the last decade, Raman Spectroscopy has demonstrated to be a label-free and non-destructive optical spectroscopy able to improve diagnostic accuracy in cancer diagnosis. This is because Raman spectroscopic measurements can reveal a deep molecular understanding of the biochemical changes in cancer tissues in comparison with non-cancer tissues. In this pilot study, we apply Raman spectroscopy imaging to the diagnosis and grading of chondrogenic tumors, including enchondroma and chondrosarcomas of increasing histologic grades. The investigation included the analysis of areas of 50×50 μm 2 to approximately 200×200 μm 2 , respectively. Multivariate statistical analysis, based on unsupervised (Principal Analysis Components) and supervised (Linear Discriminant Analysis) methods, differentiated between the various tumor samples, between cells and extracellular matrix, and between collagen and non-collagenous components. The results dealt out basic biochemical information on tumor progression giving the possibility to grade with certainty the malignant cartilaginous tumors under investigation. The basic processes revealed by Raman Spectroscopy are the progressive degrading of collagen type-II components, the formation of calcifications and the cell proliferation in tissues ranging from enchondroma to chondrosarcomas. This study highlights that Raman spectroscopy is particularly effective when cartilaginous tumors need to be subjected to histopathological analysis. Cancer diagnosis remains one of the biggest challenges in medicine. The development of new noninvasive strategies or the improvements of existing ones makes Raman Spectroscopy (RS) fundamental for diagnosing the chemical compositions of cells and tissues. RS is able to probe fundamentals vibrational states of biomolecules, and exploits a label-free and non-destructive optical approach. RS is thus being used more and more frequently to analyses biological tissues 1-6. In fact, for various types of cancers, in vivo biopsy imaging and histopathological analyses are carried out using RS 7-11. RS is also exploited to evaluate the biochemical attributes of bones, and has revealed pathological changes in the components of the bone matrices. These changes include alterations in phosphate, carbonate and collagen degradation, as well as spectral changes in terms of bone metastasis primed by prostate and breast cancer 11-13. With these abilities, the application of RS to the early diagnosis of bone tumors is more than ever necessary. In the present pilot study, we apply the RS spectral imaging technique to improve non-destructive diagnosis and grading of chondrogenic tumors. Cartilaginous tumors are the most frequent primary bone tumors. While the true incidence of enchondromas (ECs) is difficult to determine because they are often asymptomatic, central chondrosarcoma (CS) accounts for approximately 20% of malignant bone tumors 14 , with an incidence, for example, of 8.78 per million inhabitants between 2005 and 2013 in the Netherlands 15 , whereas the overall rate inci...

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Section: Discussionmentioning

confidence: 99%

Contribution of Raman Spectroscopy to Diagnosis and Grading of Chondrogenic Tumors

D’Acunto

Gaeta

Capanna

et al. 2020

Sci Rep

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“…High levels of proline could promote cell proliferation, energy production and resistance to oxidative stress (act as an antioxidant) [16][17][18][19]. L-valine is an essential and important functional amino acid involved in many growth and metabolic processes, and is also a glucogenic amino acid for biosynthesizing macromolecules (e.g., proteins and lipids), which are vital to the growth of cancer cell [20]. The accumulation of amino acids could ascribe to the proliferation by cancer cells, suggesting cancer transformation is linked with adaptive increases in protein synthesis [21].…”

Section: Discussionmentioning

confidence: 99%

Metabolomic profiling on plasma reveals potential biomarkers for screening and early diagnosis of intestinal-type gastric cancer and precancerous stages

Xiao

et al. 2020

Preprint

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Background: Gastric cancer (GC) with majority of intestinal-type adenocaricinoma remains one of the most common cancers all over the world. GC faces a great challenge in the clinical diagnosis, that it often can be detected at advanced stages, and leads to the loss of optimum time for treatment and poor prognosis. Thus, there is a critical need to develop effective and noninvasive strategies for early diagnosis of the disease process. Methods: Totally, 82 participants were enrolled in the study, including 50 chronic superficial gastritis (CSG) patients, 7 intestinal-type early gastric cancer (EGC) and 25 intestinal-type advanced gastric cancer (AGC) ones. Metabolites profiling on patient plasma was performed using ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Principal components analysis, orthogonal partial least squares-discriminant analysis as well as Random forest were utilized to evaluate the variation on endogenous metabolites for intestinal-type GC patients and to screen potential biomarkers. Furthermore, the proposed biomarkers were used to create logistic regression models, which discrimination efficiency and accuracy was ascertained by receiver operating characteristic curve (ROC) analysis. Metabolic pathway analysis were carried out on MetaboAnalyst.Results: Totally 50 metabolites were detected with differentially expression among CSG, intestinal-type EGC and AGC patients. L-carnitine, L-proline, pyruvaldehyde, phosphatidylcholines (PC) (14:0/18:0), lysophosphatidylcholine (14:0) (LysoPC 14:0), lysinoalanine were defined as the potential biomarker panel for the diagnosis among CSG and EGC patients. Compared with EGC patients, 6 significantly changed metabolites, PC(O-18:0/0:0) and LysoPC(20:4(5Z,8Z,11Z,14Z)) were found to be up-regulated in AGC patients, whereas L-proline, L-valine, adrenic acid and pyruvaldehyde down-regulated. ROC analysis demonstrated a high diagnostic performance for metabolite panels with area under the curve (AUC) of 0.931 to 1. Moreover, the metabolomic pathway analysis revealed several metabolism pathway disorder, including amino acid and lipid metabolisms, in intestinal-type GC patients.Conclusions: In this study, a total of six metabolites were identified to contribute significantly to the diagnosis of intestinal-type GC and precancerous stages, respectively, and over 93.1% AUC value was achieved in AUC test on biomarker panels, It indicated that the biomarker panels are· sensitive to the early diagnosis of intestinal-type GC disease, which is expected to be developed as a promising diagnostic and prognostic tool for disease stratification studies.

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“…Furthermore, ROS can participate in the regulation of different signaling pathways and epigenetic mechanisms. In cancer, it has been shown that enzymes involved in proline biosynthesis are dysregulated, promoting an increase in proline, which impacts upon exacerbated tumor growth [30][31][32][33][34].…”

Section: Introductionmentioning

confidence: 99%

Non-Coding RNAs as Key Regulators of Glutaminolysis in Cancer

Ortiz-Pedraza

Muñoz-Bello

Olmedo-Nieva

et al. 2020

IJMS

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Cancer cells exhibit exacerbated metabolic activity to maintain their accelerated proliferation and microenvironmental adaptation in order to survive under nutrient-deficient conditions. Tumors display an increase in glycolysis, glutaminolysis and fatty acid biosynthesis, which provide their energy source. Glutamine is critical for fundamental cellular processes, where intermediate metabolites produced through glutaminolysis are necessary for the maintenance of mitochondrial metabolism. These include antioxidants to remove reactive oxygen species, and the generation of the nonessential amino acids, purines, pyrimidines and fatty acids required for cellular replication and the activation of cell signaling. Some cancer cells are highly dependent on glutamine consumption since its catabolism provides an anaplerotic pathway to feed the Krebs cycle. Intermediate members of the glutaminolysis pathway have been found to be deregulated in several types of cancers and have been proposed as therapeutic targets and prognostic biomarkers. This review summarizes the main players in the glutaminolysis pathway, how they have been found to be deregulated in cancer and their implications for cancer maintenance. Furthermore, non-coding RNAs are now recognized as new participants in the regulation of glutaminolysis; therefore, their involvement in glutamine metabolism in cancer is discussed in detail.Int. J. Mol. Sci. 2020, 21, 2872 2 of 26 an increased glucose consumption in relation to normal differentiated tissues. Now we know that glutamine metabolism is as important as glucose metabolism for the production of macromolecules in cancer [1].Glutamine is an abundant amino acid involved in energy production, homeostasis in pro/antioxidant species and the activation of signaling pathways in cancer. In addition to the antioxidant glutathione (GSH), nucleotides, lipids and amino acids are formed from glutamine metabolism. All of these are needed for many metabolic functions such as growth, proliferation, cell survival and defense against oxidative stress [2]. Glutamine contributes, with reduced nitrogen, to the de novo biosynthesis of diverse nitrogen-containing compounds, such as purine and pyrimidine nucleotides, glucosamine-6-phosphate and nonessential amino acids.As glutamine is the most abundant amino acid in the blood and muscle tissue, normal proliferating cells use glutamine metabolism as an energy source, mediated by its catabolic products, glutamate and α-ketoglutarate (α-kG), the latter being an intermediate of the tricarboxylic acid cycle (TCA) or Krebs cycle [3]. In 1950, Harry Eagle observed that HeLa tumor cells require an excess of glutamine, in relation to other amino acids in the culture medium, for optimal growth. Furthermore, it has been reported that tumors consume glutamine faster than the surrounding normal tissue [4]. Moreover, most cancer cells are dependent on glutamine being unable to survive under glutamine starvation, an effect that has been termed glutamine addiction [5]. Various types of cancers are high...

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Proline Metabolism in Cell Regulation and Cancer Biology: Recent Advances and Hypotheses

Abstract: The proline metabolic axis can serve as a scaffold on which a variety of regulatory mechanisms are integrated. Once understood as a central mechanism in cancer metabolism, proline metabolism may be a good target for adjunctive cancer therapy.-Antioxid. Redox Signal. 00, 000-000.

Cited by 202 publications

References 105 publications

Contribution of Raman Spectroscopy to Diagnosis and Grading of Chondrogenic Tumors

Contribution of Raman Spectroscopy to Diagnosis and Grading of Chondrogenic Tumors

Metabolomic profiling on plasma reveals potential biomarkers for screening and early diagnosis of intestinal-type gastric cancer and precancerous stages

Non-Coding RNAs as Key Regulators of Glutaminolysis in Cancer

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