Analysis of glycosphingolipids of human head and neck carcinomas with comparison to normal tissue

Bolot, G.; David, M.; Taki, Takao; Handa, Shizuo; Kasama, Takeshi; Richard, Michel; Pignat, J.-C.; Thomas, Lewis; Portoukalian, Jacques

doi:10.1080/15216549800203632

Cited by 10 publications

(16 citation statements)

References 8 publications

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“…In order to elucidate the reasons for selectivity it is important to specify the factors that influence drug uptake and retention in the tissue. These factors are expected to be connected with the differences observed between normal and tumor tissue, for example pH (5)(6)(7)(8), surface charge (9)(10)(11)(12)(13) density lipoprotein receptors (14,15). Since most photosensitizers used in PDT are porhyrin-type molecules possessing sites of protonation/deprotonation in their molecular structures, it is reasonable to consider pH as one of the most important factors.…”

Section: Introductionmentioning

confidence: 99%

pH-Dependent Spectral Properties of HpIX, TPPS2a, mTHPP and mTHPC¶

Čunderlı́ková¹,

Bjørklund²,

Pettersen³

et al. 2007

Photochemistry and Photobiology

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Lower extracellular pH in tumors as compared to normal tissues has been proposed to be a factor contributing to the tumor selective uptake of several photosensitizers. Therefore, the pH dependence of absorption and fluorescence spectral properties of four different drugs relevant for photodynamic therapy (hematoporphyrin IX [HpIX], disulfonated meso‐tetraphenylporphine [TPPS2a], meso‐tetra(3‐hydroxyphenyl)porphine [mTHPP] and meso‐tetra(3‐hydroxyphenyl)chlorin [mTHPC]) has been examined. Spectral analysis of the dyes dissolved in phosphate buffered saline (PBS) indicates pH‐dependent modification in the physiologically important region (6.0–8.0) only in the case of HpIX. This modification is probably related to the protonation of carboxylic groups. Spectral changes of HpIX in PBS observed at acidic pH values <5, as well as those of the rest of the drugs (inflection points of titration curves occurred at about 5.1, 3.8 and 2.4 for TPPS2a, mTHPP and mTHPC, respectively), are likely to be due to the protonation of imino nitrogens. The tumor localizing properties of mTHPP and mTHPC reported in the literature appear to be due to factors other than pH‐dependent changes in the lipophilicity of the drugs.

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Section: Introductionmentioning

confidence: 99%

pH-Dependent Spectral Properties of HpIX, TPPS2a, mTHPP and mTHPC¶

Čunderlı́ková¹,

Bjørklund²,

Pettersen³

et al. 2007

Photochemistry and Photobiology

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“…SCC of the upper aerodigestive tract is one of the leading causes of death worldwide. Previously it was demonstrated that the sera of patients with head and neck carcinomas show tumor-size-dependent elevations of serum gangliosides [27]. In view of the role of glycosylation inhibitors, it was postulated that chemical manipulation of glycosylation can be a useful therapeutic strategy for successful chemotherapy against head and neck cancer [28].…”

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confidence: 99%

Mass spectrometric profiling of N-linked oligosaccharides and uncommon glycoform in mouse serum with head and neck tumor

Lattová

Varma

Bezabeh

et al. 2008

J. Am. Soc. Mass Spectrom.

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N-linked oligosaccharides obtained from total serum of mice with implanted head and neck tumors were analyzed and compared with those from control samples of healthy mice. Methods used include a combination of a derivatization procedure with phenylhydrazine (PHN) and analysis by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Oligosaccharides were enzymatically released from total serum with PNGaseF and purified by high-performance liquid chromatography (HPLC) on a reversed-phase column. Mass spectra contained ion peaks of labeled oligosaccharides and MS/MS experiments provided useful data for the structural elucidation of these compounds. More than 40 N-glycans with compositions characteristic of high-mannose, hybrid, complex, neutral, and sialylated structures were identified in the serum of tumoral mice. Significant differences between samples were observed with respect to the abundances of high mannose and hybrid glycans. These oligosaccharides showed higher relative intensities in the spectra obtained from the cancer sera. Complex sialylated oligosaccharides had similar abundances in both types of sera, with the exception of fucosylated biantennary disialylated oligosaccharide, which was mostly detected with lower abundance in control samples. In the MALDI spectra, several minor species corresponded to uncommon carbohydrates. These structures have been investigated in detail by MS/MS. Among these novel glycoforms, a few sialylated oligosaccharides without a free reducing end were identified. Also, glycans with an extra 60 u were observed and likely feature the presence of a 2-acetamido-2-deoxyoctose residue attached on antennae of 3-or 6-linked mannose. . It has been recognized that altered glycosylation is an universal feature of living cells and several studies have demonstrated that the changes in cellular glycosylation profiles can be also related to aggressive cancer cell behavior, such as tumor cell invasion and metastasis [2][3][4][5][6][7][8]. As cancer cells can produce oligosaccharides that are significantly different from those in normal cells, comparative studies between glycoprotein carbohydrates produced by malignant cells and normal cells may provide useful information for diagnosis, prognosis, and immunotherapy of tumors [9].Mass spectrometry (MS) has been used extensively as the most sensitive method for the analysis of carbohydrate molecules [10 -14]. Moreover, modern MS instruments allow the measurement of unseparated mixtures, and make possible the identification of trace amounts of glycans in biological materials [15]. Nonetheless, biochemical analysis of carbohydrates is generally complicated, not only because of their lower concentration relative to with proteins, but also because of the structural diversity of molecules, anomericity, linkage positions, and branching patterns of monosaccharides. Moreover, carboxylic groups cause sialylated oligosaccharides to ionize with less efficiency than neutral oligosaccharides, making MS analysis of glycans more difficu...

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“…The only two articles, of the same group, that assessed GSL expression in carcinoma cells compared to head and neck normal tissue, leave doubts as to the histological type and the anatomic sites of the tumors studied; besides, the small number of tumors studied by this group, six cases only, do not correctly represent SCC GSL expression 21,22 . Another description of SCC GSL expression profile was carried out when they studied GSL expression during the differentiation process in SCC cells in the retromolar region 20 .…”

Section: Discussionmentioning

confidence: 99%

“…However, as far as head and neck SCC (squamous cell carcinoma), especially in upper airways and digestive tracts, there are few papers showing GSL expression in the SCC differentiation or malignant transformation, despite the fact that one of the first antibodies developed against GSL be able to identify SCC LacCer 1,15 . Only Bolot et al (1998Bolot et al ( , 1999 assessed GSL expression in head and neck carcinoma and normal tissue cells, notwithstanding these papers leave doubts in regards of histologic types and the anatomical sites of the tumors studied.…”

Section: Introductionmentioning

confidence: 99%

Expressão de glicoesfingolipídeos no carcinoma espinocelular do trato aerodigestivo superior

Filho

Walder

Takahashi

et al. 2006

Rev. Bras. Otorrinolaringol.

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Os glicoesfingolipídios (GSLs) são importantes componentes da membrana celular, organizados em microdomínios, relacionados a receptores de membrana e comportamento anti-social da célula neoplásica como crescimento descontrolado, invasão e ocorrência de metástases. OBJETIVO: Como a expressão de GSLs no carcinoma espinocelular (CEC) é tema pouquíssimo estudado decidiu-se realizar estudo prospectivo visando avaliar a expressão de GSLs no CEC do trato aerodigestivo superior. MÉTODO: Coletou-se 33 amostras de CEC e mucosa normal e GSLs extraídos e purificados por cromatografia de fase reversa em coluna de C-18 e hidrólise alcalina em metanol. Os GSLs foram quantificados por densitometria das placas de cromatografia de alta resolução em camada delgada coradas com orcinol. RESULTADOS: Observou-se aumento significativo de GSLs no CEC (3,57µg/mg) em comparação à mucosa normal (1,92µg/mg), principalmente do monosialogangliosídeo (GM3), trihexosilceramida (CTH), dihexosilceramida (CDH), globosídeo (Gb4). A expressão de monohexosilceramida (CMH) foi semelhante no CEC e na mucosa normal. O aumento do GM3 no CEC foi demonstrado por métodos imunoquímicos empregando-se MAb DH2 (anti-GM3). Analisando-se os carboidratos do CMH por cromatografia gasosa acoplado a espectrômetro de massa constatou-se que a mucosa normal expressa glucosilceramida e o CEC glucosilceramida e galactosilceramida. CONCLUSÃO: O aumento de GSLs no tecido tumoral pode representar alterações dos microdomínios da membrana celular resultantes do processo de transformação maligna, responsáveis por uma maior interação célula-célula e célula-matriz aumentando seu potencial de infiltração e metástase, possibilitando o emprego dos GSLs e de MAbs no diagnóstico e no tratamento do CEC, a exemplo do que ocorre no melanoma.

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Analysis of glycosphingolipids of human head and neck carcinomas with comparison to normal tissue

Cited by 10 publications

References 8 publications

pH-Dependent Spectral Properties of HpIX, TPPS2a, mTHPP and mTHPC¶

pH-Dependent Spectral Properties of HpIX, TPPS2a, mTHPP and mTHPC¶

Mass spectrometric profiling of N-linked oligosaccharides and uncommon glycoform in mouse serum with head and neck tumor

Expressão de glicoesfingolipídeos no carcinoma espinocelular do trato aerodigestivo superior

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