Expression and potential role of apolipoprotein D on the death–survival balance of human colorectal cancer cells under oxidative stress conditions

Bajo‐Grañeras, Raquel; Crespo‐Sanjuán, Jesús; García-Centeno, Rosa M.; Garrote, José Antonio; Gutiérrez, Gabriel; García-Tejeiro, M.; Aguirre-Gervás, Beatriz; Calvo-Nieves, María Dolores; Bustamante, Rosa; Ganfornina, Marı́a D.; Sánchez, Diego

doi:10.1007/s00384-012-1616-2

Cited by 29 publications

(28 citation statements)

References 49 publications

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“…Another apolipoprotein (APOD) manifests contradictory and highly unusual behavior. The inverse correlation of APOD with tumor progression, particularly in the CRC case, is a known phenomenon [69,70]. According to these studies, our finding of FC = 1.49 assumingly corresponds to the early stages (I and II) of cancer development.…”

Section: The Prognostic Significance Of Lipid Metabolismsupporting

confidence: 60%

Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development

et al. 2020

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Background: Colorectal cancer (CRC) at a current clinical level is still hardly diagnosed, especially with regard to nascent tumors, which are typically asymptotic. Searching for reliable biomarkers of early diagnosis is an extremely essential task. Identification of specific post-translational modifications (PTM) may also significantly improve net benefits and tailor the process of CRC recognition. We examined depleted plasma samples obtained from 41 healthy volunteers and 28 patients with CRC at different stages to conduct comparative proteome-scaled analysis. The main goal of the study was to establish a constellation of protein markers in combination with their PTMs and semi-quantitative ratios that may support and realize the distinction of CRC until the disease has a poor clinical manifestation. Results: Proteomic analysis revealed 119 and 166 proteins for patients in stages I–II and III–IV, correspondingly. Plenty of proteins (44 proteins) reflected conditions of the immune response, lipid metabolism, and response to stress, but only a small portion of them were significant (p < 0.01) for distinguishing stages I–II of CRC. Among them, some cytokines (Clusterin (CLU), C4b-binding protein (C4BP), and CD59 glycoprotein (CD59), etc.) were the most prominent and the lectin pathway was specifically enhanced in patients with CRC. Significant alterations in Inter-alpha-trypsin inhibitor heavy chains (ITIH1, ITIH2, ITIH3, and ITIH4) levels were also observed due to their implication in tumor growth and the malignancy process. Other markers (Alpha-1-acid glycoprotein 2 (ORM2), Alpha-1B-glycoprotein (A1BG), Haptoglobin (HP), and Leucine-rich alpha-2-glycoprotein (LRG1), etc.) were found to create an ambiguous core involved in cancer development but also to exactly promote tumor progression in the early stages. Additionally, we identified post-translational modifications, which according to the literature are associated with the development of colorectal cancer, including kininogen 1 protein (T327-p), alpha-2-HS-glycoprotein (S138-p) and newly identified PTMs, i.e., vitamin D-binding protein (K75-ac and K370-ac) and plasma protease C1 inhibitor (Y294-p), which may also contribute and negatively impact on CRC progression. Conclusions: The contribution of cytokines and proteins of the extracellular matrix is the most significant factor in CRC development in the early stages. This can be concluded since tumor growth is tightly associated with chronic aseptic inflammation and concatenated malignancy related to loss of extracellular matrix stability. Due attention should be paid to Apolipoprotein E (APOE), Apolipoprotein C1 (APOC1), and Apolipoprotein B-100 (APOB) because of their impact on the malfunction of DNA repair and their capability to regulate mTOR and PI3K pathways. The contribution of the observed PTMs is still equivocal, but a significant decrease in the likelihood between modified and native proteins was not detected confidently.

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Section: The Prognostic Significance Of Lipid Metabolismsupporting

confidence: 60%

Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development

et al. 2020

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“…The peak of apoD production also correlated with increased apoptosis, as assessed by TUNEL labelling. Increased apoD expression has been reported in pathologic conditions with increased apoptosis and a potential role of apoD on the deathsurvival balance was suggested [59].…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein D Overexpression Protects Against Kainate-Induced Neurotoxicity in Mice

et al. 2016

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Excitotoxicity due to the excessive activation of glutamatergic receptors leads to neuronal dysfunction and death. Excitotoxicity has been implicated in the pathogenesis of a myriad of neurodegenerative diseases with distinct etiologies such as Alzheimer's and Parkinson's. Numerous studies link apolipoprotein D (apoD), a secreted glycoprotein highly expressed in the central nervous system (CNS), to maintain and protect neurons in various mouse models of acute stress and neurodegeneration. Here, we used a mouse model overexpressing human apoD in neurons (H-apoD Tg) to test the neuroprotective effects of apoD in the kainic acid (KA)-lesioned hippocampus. Our results show that apoD overexpression in H-apoD Tg mice induces an increased resistance to KA-induced seizures, significantly attenuates inflammatory responses and confers protection against KA-induced cell apoptosis in the hippocampus. The apoD-mediated protection against KA-induced toxicity is imputable in part to increased plasma membrane Ca2+ ATPase type 2 expression (1.7-fold), decreased N-methyl-D-aspartate receptor (NMDAR) subunit NR2B levels (30 %) and lipid metabolism alterations. Indeed, we demonstrate that apoD can attenuate intracellular cholesterol content in primary hippocampal neurons and in brain of H-apoD Tg mice. In addition, apoD can be internalised by neurons and this internalisation is accentuated in ageing and injury conditions. Our results provide additional mechanistic information on the apoD-mediated neuroprotection in neurodegenerative conditions.

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“…ApoD promoter is basally methylated in HT-29 cells but retains the ability to respond to OS. Exogenous addition of ApoD to HT-29 cells does not modify proliferation or apoptosis levels in control conditions, but it promotes apoptosis upon paraquat-induced oxidative stress [50].…”

Section: Apod and Tumor Pathologymentioning

confidence: 87%

“…Besides using ApoD as marker of initial stages of tumor progression, it can become a therapeutic tool promoting death of proliferating tumor cells suffering oxidative stress [50].…”

Section: Apod and Tumor Pathologymentioning

confidence: 99%

Apolipoprotein D

Crespo‐Sanjuán¹,

Zamora-Gonzalez²,

Calvo-Nieves³

et al. 2017

Advances in Lipoprotein Research

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Apolipoprotein D (ApoD) is an extracellular glycoprotein of the lipocalin protein family, involved in different functions such as immune response, cell proliferation regulation, chemoreception, retinoid metabolism, axon growth, and proteolysis regulation. This lipocalin is expressed predominantly in the nervous system (NS), both prenatally (vascular pericytes) and postnatally (glia and neurons) and in adulthood. It is also expressed in other tissues and is carried by high-density lipoprotein (HDL) in plasma, so it could interfere in cholesterol and other lipids regulation. ApoD increases considerably in systemic apocrine gland tumors and also in some primary brain tumors. Although the specific biological role of ApoD is unknown, the presence of ApoD in tumors appears to be a prognostic factor in their evolution. Regarding the NS, increased ApoD expression observed in many neurodegenerative diseases could be used to make an early diagnosis thereof.

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Expression and potential role of apolipoprotein D on the death–survival balance of human colorectal cancer cells under oxidative stress conditions

Cited by 29 publications

References 49 publications

Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development

Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development

Apolipoprotein D Overexpression Protects Against Kainate-Induced Neurotoxicity in Mice

Apolipoprotein D

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