Mass spectrometry and the cellular surfaceome

Pauwels, Jarne; Fijałkowska, Daria; Eyckerman, Sven; Gevaert, Kris

doi:10.1002/mas.21690

Cited by 28 publications

(23 citation statements)

References 326 publications

(361 reference statements)

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“…Although versatile, the purification of biotinylated surface proteins remains prone to contaminations from associated protein complexes and unspecific protein interactions ( 36 , 37 ). This has generated numerous surfaceome catalogs for LC-MS/MS data filtering based on bioinformatic annotations from RNA data ( 1 , 38 ) or combined with experimental proteomics data from 2D cell cultures ( 1 , 39 – 42 ).…”

Section: Discussionmentioning

confidence: 99%

Landscape of surfaceome and endocytome in human glioma is divergent and depends on cellular spatial organization

Governa

Talbot

Oliveira

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Therapeutic strategies directed at the tumor surfaceome (TS), including checkpoint inhibitor blocking antibodies, antibody drug conjugates (ADCs), and chimeric antigen receptor T (CAR-T) cells, provide a new armament to fight cancer. However, a remaining bottleneck is the lack of strategies to comprehensively interrogate patient tumors for potential TS targets. Here, we have developed a platform (tumor surfaceome mapping [TS-MAP]) integrated with a newly curated TS classifier (SURFME) that allows profiling of primary 3D cultures and intact patient glioma tumors with preserved tissue architecture. Moreover, TS-MAP specifically identifies proteins capable of endocytosis as tractable targets for ADCs and other modalities requiring toxic payload internalization. In high-grade gliomas that remain among the most aggressive forms of cancer, we show that cellular spatial organization (2D vs. 3D) fundamentally transforms the surfaceome and endocytome (e.g., integrins, proteoglycans, semaphorins, and cancer stem cell markers) with general implications for target screening approaches, as exemplified by an ADC targeting EGFR. The TS-MAP platform was further applied to profile the surfaceome and endocytome landscape in a cohort of freshly resected gliomas. We found a highly diverse TS repertoire between patient tumors, not directly associated with grade and histology, which highlights the need for individualized approaches. Our data provide additional layers of understanding fundamental to the future development of immunotherapy strategies, as well as procedures for proteomics-based target identification and selection. The TS-MAP platform should be widely applicable in efforts aiming at a better understanding of how to harness the TS for personalized immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Landscape of surfaceome and endocytome in human glioma is divergent and depends on cellular spatial organization

Governa

Talbot

Oliveira

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…However, the identification of GPCRs by immunolabeling is difficult, due to the small exposed area of extracellular epitopes and very high conformational variability. Conventional mass spectrometry is also challenging, as receptors are not readily isolatable from membranes [299][300][301].…”

Section: Limitation Of Available Toolsmentioning

confidence: 99%

Targeting GPCRs and Their Signaling as a Therapeutic Option in Melanoma

Raymond

Aktary

Larue

et al. 2022

Cancers

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G-protein-coupled receptors (GPCRs) serve prominent roles in melanocyte lineage physiology, with an impact at all stages of development, as well as on mature melanocyte functions. GPCR ligands are present in the skin and regulate melanocyte homeostasis, including pigmentation. The role of GPCRs in the regulation of pigmentation and, consequently, protection against external aggression, such as ultraviolet radiation, has long been established. However, evidence of new functions of GPCRs directly in melanomagenesis has been highlighted in recent years. GPCRs are coupled, through their intracellular domains, to heterotrimeric G-proteins, which induce cellular signaling through various pathways. Such signaling modulates numerous essential cellular processes that occur during melanomagenesis, including proliferation and migration. GPCR-associated signaling in melanoma can be activated by the binding of paracrine factors to their receptors or directly by activating mutations. In this review, we present melanoma-associated alterations of GPCRs and their downstream signaling and discuss the various preclinical models used to evaluate new therapeutic approaches against GPCR activity in melanoma. Recent striking advances in our understanding of the structure, function, and regulation of GPCRs will undoubtedly broaden melanoma treatment options in the future.

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“…An alternative to transcriptional analysis is likely being the identification of GPCRs at metastatic sites on the basis of protein expression. However, the identification of GPCRs by immunolabeling is difficult, due to the small exposed area of extracellular epitopes and very high conformational variability, or by conventional mass spectrometry, as receptors are not readily isolatable from membranes [290][291][292].…”

Section: A Limitation Of Available Toolsmentioning

confidence: 99%

“…The major limitation in the high-throughput identification of GPCRs via mass spectrometry is the depletion of GPCRs from mass spectrometry samples. This bias can be avoided by performing surfaceomes, which will significantly enrich samples for membrane glycoproteins and thus potentially reveal the expression of GPCRs [292,294,295]. Finally, GPCRs can also be indirectly identified by analyzing cell-binding ligands rather than the receptors directly [296].…”

Section: A Limitation Of Available Toolsmentioning

confidence: 99%

Targeting GPCRs & their Signaling as a Therapeutic Option in Melanoma

Raymond¹,

Aktary²,

Larue³

et al. 2022

Preprint

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G protein-coupled receptors (GPCRs) serve prominent roles in melanocyte lineage physiology, with an impact at all stages of development, as well as on mature melanocyte functions. GPCR ligands are present in the skin and regulate melanocyte homeostasis, including pigmentation. The role of GPCRs in the regulation of pigmentation and, consequently, protection against external aggression, such as ultraviolet radiation, has long been established. However, evidence of new functions of GPCRs directly in melanomagenesis has been highlighted in recent years. GPCRs are coupled, through their intracellular domains, to heterotrimeric G proteins, which induce cellular signaling through various pathways. Such signaling modulates essential cellular processes of melanomagenesis, such as proliferation and migration. GPCR-associated signaling in melanoma can be activated by the binding of paracrine factors to their receptors or directly by activating mutations. In this review, we present melanoma-associated alterations of GPCRs and their downstream signaling and discuss the various preclinical models used to evaluate new therapeutic approaches against GPCR activity in melanoma. Recent striking advances in our understanding of the structure, function, and regulation of GPCRs will undoubtedly broaden treatment options in melanoma in the future.

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Mass spectrometry and the cellular surfaceome

Cited by 28 publications

References 326 publications

Landscape of surfaceome and endocytome in human glioma is divergent and depends on cellular spatial organization

Landscape of surfaceome and endocytome in human glioma is divergent and depends on cellular spatial organization

Targeting GPCRs and Their Signaling as a Therapeutic Option in Melanoma

Targeting GPCRs & their Signaling as a Therapeutic Option in Melanoma

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