Role of tumor cell surface lysosome-associated membrane protein-1 (LAMP1) and its associated carbohydrates in lung metastasis

Agarwal, Akhil Kumar; Srinivasan, Nithya; Godbole, Rashmi; More, Shyam K.; Budnar, Srikanth; Gude, Rajiv P.; Kalraiya, Rajiv D.

doi:10.1007/s00432-015-1917-2

Cited by 43 publications

(33 citation statements)

References 41 publications

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“…Our studies on a number of cancer cell lines proved that LAMPs on the cell surface served as adhesive glycoproteins participating in the complex process of tumor invasion and metastasis . This idea was supported by evidence for surface LAMP‐1 that promotes interactions with the extracellular matrix and basement membrane thus facilitating lung metastasis in melanoma . The overexpression of LAMP‐1 in our cases might reflect high metastatic potential of the tumor.…”

Section: Discussionsupporting

confidence: 72%

LAMP‐1 gene is overexpressed in high grade glioma

Sarafian

Koev²,

Mehterov

et al. 2018

APMIS

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High-grade gliomas (HGG) are the most frequent brain tumors in adults. Glioblastoma multiforme (GBM) is their most aggressive form resistant to therapy. It was shown that inhibition of autophagy reduced GBM development and autophagy interfering agents are regarded as a new strategy to fight glioma cells. The lysosome-associated membrane proteins (LAMPs) display differential expression particularly in cancer. There are few data on their expression and especially on their molecular profile. The aim of the present study is to investigate the expression of LAMP-1 and LAMP-2 genes and proteins in HGG. Newly diagnosed patients with HGG and healthy controls were examined by immunohistochemistry and qPCR for both protein and mRNA levels of LAMP-1 and LAMP-2. The transcriptional activity of LAMP-1 in HGG was significantly higher compared to normal brain and to LAMP-2. The two glycoproteins were detected in the cytosol of tumor cells with varying intensity, LAMP-1 showing again enhanced expression. In conclusion, novel data on LAMP-1 overexpression in HGG are presented suggesting involvement of this gene and protein in cell adhesion and tumor progression. These findings might help the elucidation of the complex biological role of the multifunctional LAMPs proteins and to predict novel therapeutic targets in lysosomes.

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Section: Discussionsupporting

confidence: 72%

LAMP‐1 gene is overexpressed in high grade glioma

Sarafian

Koev²,

Mehterov

et al. 2018

APMIS

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“…LAMP1 encodes a glycoprotein and is responsible for maintaining lysosomal integrity. The expression of LAMP1 has been observed on the surface of tumor cells from highly metastatic cancers, suggesting its role in the progression of lung cancer, colon cancer, and melanoma [60]. Surprisingly, LAMP2, another glycoprotein closely related to LAMP1, was up-regulated in BDE-99 exposed cells ( Fig 8D).…”

Section: Enriched Canonical Pathways Following Exposure To Bde-99mentioning

confidence: 91%

Transcriptomic profiling of PBDE-exposed HepaRG cells unveils critical lncRNA- PCG pairs involved in intermediary metabolism

Zhang

Kelly

et al. 2020

PLoS ONE

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Polybrominated diphenyl ethers (PBDEs) were formally used as flame-retardants and are chemically stable, lipophlic persistent organic pollutants which are known to bioaccumulate in humans. Although its toxicities are well characterized, little is known about the changes in transcriptional regulation caused by PBDE exposure. Long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators of transcriptional and translational processes. It is hypothesized that lncRNAs can regulate nearby protein-coding genes (PCGs) and changes in the transcription of lncRNAs may act in cis to perturb gene expression of its neighboring PCGs. The goals of this study were to 1) characterize PCGs and lncRNAs that are differentially regulated from exposure to PBDEs; 2) identify PCG-lncRNA pairs through genome annotation and predictive binding tools; and 3) determine enriched canonical pathways caused by differentially expressed lncRNA-PCGs pairs. HepaRG cells, which are humanderived hepatic cells that accurately represent gene expression profiles of human liver tissue, were exposed to BDE-47 and BDE-99 at a dose of 25 μM for 24 hours. Differentially expressed lncRNA-PCG pairs were identified through DESeq2 and HOMER; significant canonical pathways were determined through Ingenuity Pathway Analysis (IPA). LncTar was used to predict the binding of 19 lncRNA-PCG pairs with known roles in drug-processing pathways. Genome annotation revealed that the majority of the differentially expressed lncRNAs map to PCG introns. PBDEs regulated overlapping pathways with PXR and CAR such as protein ubiqutination pathway and peroxisome proliferator-activated receptor alpharetinoid X receptor alpha (PPARα-RXRα) activation but also regulate distinctive pathways involved in intermediary metabolism. PBDEs uniquely down-regulated GDP-L-fucose biosynthesis, suggesting its role in modifying important pathways involved in intermediary metabolism such as carbohydrate and lipid metabolism. In conclusion, we provide strong evidence that PBDEs regulate both PCGs and lncRNAs in a PXR/CAR ligand-dependent and independent manner.

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“…LAMP1 (CD107a) is a member of a family of membrane glycoproteins, expressed in all tissue types. Previous studies demonstrated that LAMP proteins mediate cell adhesion, migration and cancer metastasis (73,74). CD59, another candidate for further validation, is a GPI-anchored and lipid raft-localized glycoprotein of the LY6/uPAR family, similar to TEX101.…”

Section: Discussionmentioning

confidence: 99%

Discovery of a Human Testis-specific Protein Complex TEX101-DPEP3 and Selection of Its Disrupting Antibodies

Schiza

Korbakis

Panteleli

et al. 2018

Molecular & Cellular Proteomics

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TEX101 is a testis-specific protein expressed exclusively in male germ cells and is a validated biomarker of male infertility. Studies in mice suggest that TEX101 is a cell-surface chaperone which regulates, through protein-protein interactions, the maturation of proteins involved in spermatozoa transit and oocyte binding. Male TEX101-null mice are sterile. Here, we identified by co-immunoprecipitation-mass spectrometry the interactome of human TEX101 in testicular tissues and spermatozoa. The testis-specific cell-surface dipeptidase 3 (DPEP3) emerged as the top hit. We further validated the TEX101-DPEP3 complex by using hybrid immunoassays.Combinations of antibodies recognizing different epitopes of TEX101 and DPEP3 facilitated development of a simple immunoassay to screen for disruptors of TEX101-DPEP3 complex. As a proof-of-a-concept, we demonstrated that anti-TEX101 antibody T4 disrupted the native TEX101-DPEP3 complex. Disrupting antibodies may be used to study the human TEX101-DPEP3 complex, and to develop modulators for male fertility.

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Role of tumor cell surface lysosome-associated membrane protein-1 (LAMP1) and its associated carbohydrates in lung metastasis

Abstract: PolyLacNAc on B16F10 cells and galectin-3 on lungs are the major participants in melanoma metastasis. Although surface LAMP1 promotes interactions with organ ECM and BM, carbohydrates on LAMP1 play a decisive role in dictating lung metastasis.

Cited by 43 publications

References 41 publications

LAMP‐1 gene is overexpressed in high grade glioma

LAMP‐1 gene is overexpressed in high grade glioma

Transcriptomic profiling of PBDE-exposed HepaRG cells unveils critical lncRNA- PCG pairs involved in intermediary metabolism

Discovery of a Human Testis-specific Protein Complex TEX101-DPEP3 and Selection of Its Disrupting Antibodies

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