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Ascites from Ovarian Cancer Induces Novel Fucosylated Proteins

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Cancer Microenvironment

Abstract

Ovarian cancer is considered to be the most lethal type of gynecological cancer. During the advanced stages of ovarian cancer, an accumulation of ascites is observed. Fucosylation has been classified as an abnormal post-translational modification that is present in many diseases, including ovarian cancer. Ovarian cancer cells that are cultured with ascites stimulation change their morphology; concomitantly, the fucosylation process is altered. However, it is not known which fucosylated proteins are modified. The goal of this work was to identify the differentially fucosylated proteins that are expressed by ovarian cancer cell lines that are cultured with ovarian cancer patients’ ascites. Aleuria aurantia lectin was used to detect fucosylation, and some changes were observed, especially in the cell membrane. Affinity chromatography and mass spectrometry (MALDI-TOF) were used to identify 6 fucosylated proteins. Four proteins (Intermediate filament family orphan 1 [IFFO1], PHD finger protein 20-like protein 1 [PHF20L1], immunoglobulin gamma 1 heavy chain variable region partial [IGHV1–2], and Zinc finger protein 224 [ZNF224]) were obtained from cell cultures stimulated with ascites, and the other two proteins (Peregrin [BRPF1] and Dystrobrevin alpha [DTNA]) were obtained under normal culture conditions. The fucosylated state of some of these proteins was further analyzed. The experimental results show that the ascites of ovarian cancer patients modulated the fucosylation process. The PHD finger protein 20-like protein 1, Zinc finger protein 224 and Peregrin proteins colocalize with fucosylation at different levels.

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Acknowledgments

We gratefully acknowledge Gabriel Martinez Batallar for mass spectrometry analysis at the laboratory of Dr. Sergio Encarnación Guevara from Centro de Ciencias Genómicas, UNAM, Mexico; Jessica Márquez Dueñas for her help in the purchase and procurement of materials.

Funding

This project was supported by a grant for Health Research (233739), from CONACYT and the Health Ministry, México; DRAA was a recipient of a PhD fellowship also from CONACYT, México (338858).

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Authors and Affiliations

  1. Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, Delegación Gustavo A. Madero, 07360, Ciudad de México, Mexico

    Dulce Rosario Alberto-Aguilar, Verónica Ivonne Hernández-Ramírez, Juan Carlos Osorio-Trujillo & Patricia Talamás-Rohana

  2. Instituto Nacional de Cancerología, Av. San Fernando No. 22, Col. Sección XVI, Delegación Tlalpan, 07360, Ciudad de México, Mexico

    Dolores Gallardo-Rincón & Alfredo Toledo-Leyva

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  1. Dulce Rosario Alberto-Aguilar
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  2. Verónica Ivonne Hernández-Ramírez
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  3. Juan Carlos Osorio-Trujillo
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Correspondence to Patricia Talamás-Rohana.

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Supplementary Figure 1

Time course of fucosylation of SKOV-3 cells treated with ascites 01 and 02. The graphs show the time course of fucosylation (arbitrary units of fluorescence expressed as fluorescence intensity) in nonpermeabilized (left panel) and permeabilized (right panel) cells. The data of three independent experiments were analyzed by one-way ANOVA in GraphPad Prism 7. (JPG 45 kb)

Supplementary Figure 2

Ascites modulate fucosylation expression in different cell lines. Membrane fucosylation was analyzed in SKOV-3 (a), OVCAR-3 (b), and Caco-2 and BEAS-2B (d) cell lines. Ascites from 10 different ovarian cancer patients were employed to stimulate the cells for 24 h. The samples were analyzed by confocal microscopy. Fucosylation was detected by biotinylated Aleuria aurantia lectin (1:200 dilution) and FITC-conjugated streptavidin (1:200 dilution). The nuclei were stained with DAPI. The selected images are representative of two independent biological replicates. The graphs show the level of fucosylation (arbitrary units of fluorescence expressed as fluorescence intensity) in SKOV-3 cells (a, lower panel) and OVCAR-3 cells (b, lower panel). The data of two independent experiments were analyzed by one-way ANOVA in GraphPad Prism 7. (JPG 2277 kb)

Supplementary Figure 3

Schematic representation of probable sites of N-glycosylation. By in silico analysis, the probable N-glycosylation sites were predicted using the NetNGlyc database. Each of the analyzed proteins is represented (each canonical isoform); the red arrows indicate the site in which the probable glycosylation may occur. The position and the value assigned are indicated next to the arrows. A potential crossing 0.5 threshold predicts glycosylation. (JPG 112 kb)

Supplementary Table 1

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Alberto-Aguilar, D.R., Hernández-Ramírez, V.I., Osorio-Trujillo, J.C. et al. Ascites from Ovarian Cancer Induces Novel Fucosylated Proteins. Cancer Microenvironment 12, 181–195 (2019). https://doi.org/10.1007/s12307-019-00227-z

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