Labyrinthin: A distinct pan-adenocarcinoma diagnostic and immunotherapeutic tumor specific antigen

Babich, Michael; Sharma, Ankit; Li, Tianhong; Radosevich, James A.

doi:10.1016/j.heliyon.2022.e08988

Cited by 5 publications

(7 citation statements)

References 79 publications

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“…Labyrinthin has been implicated as a pan-tumor marker and target [1, 5], but more information is needed about elementary attributes related to its structure. Therefore, various computer-based programs were used to evaluate labyrinthin topology (Fig.…”

Section: Data Descriptionmentioning

confidence: 99%

“…Microscopic images of immunofluorescent labelled MCA 44-3A6 binding to A549 cells at random cell cycle stages complement the FACS results and further showed labyrinthin persisted on the cell surfaces along with some cell internalization within 20 minutes. The dataset presented herein is related to research article: “Labyrinthin: A distinct pan-adenocarcinoma diagnostic and immunotherapeutic tumor specific antigen” by Babich et. al 2022, Heliyon [1].…”

mentioning

confidence: 99%

“…The dataset presented herein is related to research article: “Labyrinthin: A distinct pan-adenocarcinoma diagnostic and immunotherapeutic tumor specific antigen” by Babich et. al 2022, Heliyon [1].…”

mentioning

confidence: 99%

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Topology and adenocarcinoma cell localization dataset on the labyrinthin biomarker

Babich¹,

Sharma²,

et al. 2021

Preprint

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Structural analysis and detection of optimal cell surface localization of labyrinthin, a pan-adenocarcinoma target, was studied with respect to adenocarcinoma specificity vs. normal and non-adenocarcinoma cells. Patient-derived tissue microarray immunohistochemistry (IHC) was performed on 729 commercially prepared tissue blocks of lung, colon, breast, pancreas, prostate, and ovary cancers combined, plus a National Cancer Institute (NCI) tissue microarray derived from another 236 cases. The results confirmed that anti-labyrinthin mouse monoclonal MCA 44-3A6 antibody recognized adenocarcinomas, but not normal or non-adenocarcinoma cancer cells. The consensus of multiple topology analysis programs on labyrinthin (255 amino acids) estimate a type II cell membrane associated protein with an N-terminus signal peptide. However, because the labyrinthin sequence is enveloped within the 758 amino acids of the intracellular aspartyl/asparaginyl beta-hydroxylase (ASPH), a purported tumor associated antigen, standard IHC methods that permeabilize cells can expose common epitopes. To circumvent antibody cross-reactivity, cell surface labyrinthin was distinguished from intracellular ASPH by FACS analysis of permeabilized vs non-permeabilized cells. All permeabilized normal, adeno-and non-adenocarcinoma cells produced a strong MCA 44-3A6 binding signal, likely reflecting co-recognition of intracellular ASPH proteins along with internalized labyrinthin, but in non-permeabilized cells only adenocarcinoma cells were positive for labyrinthin. Confocal microscopy confirmed the FACS results. Labyrinthin as a functional cell-surface marker was suggested when: 1) WI-38 normal lung fibroblasts transfected with labyrinthin sense cDNA displayed a cancerous phenotype; 2) antisense transfection of A549 human lung adenocarcinoma cells appeared more normal; and 3) MCA44-3A6 suppressed A549 cell proliferation. Collectively, the data indicate that labyrinthin is a unique, promising adenocarcinoma tumor-specific antigen and therapeutic target. The study also raises a controversial issue on the extent, specificity, and usefulness of ASPH as an adenocarcinoma tumor-associated antigen.

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Section: Data Descriptionmentioning

confidence: 99%

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confidence: 99%

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Topology and adenocarcinoma cell localization dataset on the labyrinthin biomarker

Babich¹,

Sharma²,

et al. 2021

Preprint

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“…Throughout the history of cancer care, adenocarcinomas have continued to be the most common histologic type of solid tumors, mainly due to their ability to arise from nearly anywhere in the body. Labyrinthin (LAB) is a distinct pan-adenocarcinoma tumor-specific target composed of 255 amino acid (AA) proteins within the 758 AA of the intracellular aspartyl/asparaginyl beta-hydroxylase (ASPH) that was discovered in 1985 [1]. ASPH has diverse molecular functions [2].…”

Section: Introductionmentioning

confidence: 99%

Labyrinthin Expression Is Associated with Poor Prognosis in Patients with Non-Small-Cell Lung Cancer

Zeng

Montoya

et al. 2023

Cancers

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To determine Labyrinthin (LAB) expression in non-small-cell lung cancer (NSCLC), we immunostained and scored for LAB immunohistochemistry (IHC) expression on sections of tissue microarrays (TMAs) prepared from 256 archival tissue blocks of NSCLC. Propensity-score-weighted Kaplan–Meier curves and weighted Cox models were used to associate LAB expression with overall survival. LAB mRNA expression was assessed in The Cancer Genome Atlas (TCGA) and correlated with clinical phenotype and outcome. Positive LAB IHC expression (>5% of tumor cells) was detected in 208/256 (81.3%) of NSCLC samples, and found in both lung adenocarcinomas (LUAD) and lung squamous cell cancer (LUSC). LAB positivity was associated with poor overall survival (HR = 3.56, 95% CI: 2.3–5.4; p < 0.0001) and high tumor differentiation grade or metastasis compared with negative LAB expression. Univariant and multivariate survival analyses demonstrated LAB expression as an independent prognostic factor for NSCLC patients. LAB RNA expression in TCGA-LUAD was higher in primary and advanced-stage tumors than in normal tissue, and was associated with poorer overall survival. No significant differences or associations were found with LAB RNA expression in TCGA-LUSC. The LAB IHC assay is being used to identify candidate cancer patients for the first-in-human phase I trial evaluating the LAB vaccines (UCDCC#296, NCT051013560).

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“…HAAH is not expressed in normal tissues, but highly expressed in a variety of tumor cells, including glioma ( Yang et al, 2010 ; Chen et al, 2019 ; Lin et al, 2019 ), and is regarded as a broad-spectrum tumor-associated antigen ( Zheng et al, 2020 ). It is a membrane protein expressed on the surface of tumor cells, and can be used for the accurate localization of cancer lesions ( Babich et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

The inhibitory effect of human umbilical cord mesenchymal stem cells expressing anti-HAAH scFv-sTRAIL fusion protein on glioma

Xue

Wang

et al. 2022

Front. Bioeng. Biotechnol.

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Glioma is the most common malignant intracranial tumor with low 5-year survival rate. In this study, we constructed a plasmid expressing anti-HAAH single-chain antibody and sTRAIL fusion protein (scFv-sTRAIL), and explored the effects of the double gene modified human umbilical cord mesenchyreal stem cells (hucMSCs) on the growth of glioma in vitro and in vivo. The isolated hucMSCs were identified by detecting the adipogenic differentiation ability and the osteogenic differentiation ability. The phenotypes of hucMSCs were determined by the flow cytometry. The hucMSCs were infected with lentivirus expression scFv-sTRAIL fusion protein. The expression of sTRAIL in hucMSCs were detected by immunofluorescence staining, western blot and ELISA. The tropism of hucMSCs toward U87G cells was assessed by transwell assay. The inhibitory effect of hucMSCs on U87G cells were explored by CCK8 and apoptosis assay. The xenograft tumor was established by subcutaneously injection of U87G cells into the back of mice. The hucMSCs were injected via tail veins. The inhibitory effect of hucMSCs on glioma in vivo was assessed by TUNEL assay. The hucMSCs migrated into the xenograft tumor were revealed by detecting the green fluorescent. The results showed that the scFv-sTRAIL expression did not affect the phenotypes of hucMSCs. The scFv-sTRAIL expression promoted the tropism of hucMSCs toward U87G cells, enhanced the inhibitory effect and tumor killing effect of hucMSCs on U87G cells. The in vivo study showed that hucMSCs expressing scFv-sTRAIL demonstrated significantly higher inhibitory effect and tumor killing effect than hucMSCs expressing sTRAIL. The green fluorescence intensity in the mice injected with hucMSCs expressing scFv-sTRAIL was significantly higher than that injected with hucMSCs expressing sTRAIL. These data suggested that the scFv conferred the targeting effect of hucMSCs tropism towards the xenograft tumor. In conclusion, the hucMSCs expressing scFv-sTRAIL fusion protein gained the capability to target and kill gliomas cells in vitro and in vivo. These findings shed light on a potential therapy for glioma treatment.

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Labyrinthin: A distinct pan-adenocarcinoma diagnostic and immunotherapeutic tumor specific antigen

Cited by 5 publications

References 79 publications

Topology and adenocarcinoma cell localization dataset on the labyrinthin biomarker

Topology and adenocarcinoma cell localization dataset on the labyrinthin biomarker

Labyrinthin Expression Is Associated with Poor Prognosis in Patients with Non-Small-Cell Lung Cancer

The inhibitory effect of human umbilical cord mesenchymal stem cells expressing anti-HAAH scFv-sTRAIL fusion protein on glioma

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