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High-resolution imaging mass spectrometry combined with transcriptomic analysis identified a link between fatty acid composition of phosphatidylinositols and the immune checkpoint pathway at the primary tumour site of breast cancer
BACKGROUND: The fatty acid (FA) composition of phosphatidylinositols (PIs) is tightly regulated in mammalian tissue since its disruption impairs normal cellular functions. We previously found its significant alteration in breast cancer by using matrix-assisted laser desorption and ionisation imaging...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051979/ https://www.ncbi.nlm.nih.gov/pubmed/31819188 http://dx.doi.org/10.1038/s41416-019-0662-8 |
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author | Kawashima, Masahiro Tokiwa, Mariko Nishimura, Tomomi Kawata, Yukiko Sugimoto, Masahiro Kataoka, Tatsuki R. Sakurai, Takaki Iwaisako, Keiko Suzuki, Eiji Hagiwara, Masatoshi Harris, Adrian L. Toi, Masakazu |
author_facet | Kawashima, Masahiro Tokiwa, Mariko Nishimura, Tomomi Kawata, Yukiko Sugimoto, Masahiro Kataoka, Tatsuki R. Sakurai, Takaki Iwaisako, Keiko Suzuki, Eiji Hagiwara, Masatoshi Harris, Adrian L. Toi, Masakazu |
author_sort | Kawashima, Masahiro |
collection | PubMed |
description | BACKGROUND: The fatty acid (FA) composition of phosphatidylinositols (PIs) is tightly regulated in mammalian tissue since its disruption impairs normal cellular functions. We previously found its significant alteration in breast cancer by using matrix-assisted laser desorption and ionisation imaging mass spectrometry (MALDI-IMS). METHODS: We visualised the histological distribution of PIs containing different FAs in 65 primary breast cancer tissues using MALDI-IMS and investigated its association with clinicopathological features and gene expression profiles. RESULTS: Normal ductal cells (n = 7) predominantly accumulated a PI containing polyunsaturated FA (PI-PUFA), PI(18:0/20:4). PI(18:0/20:4) was replaced by PIs containing monounsaturated FA (PIs-MUFA) in all non-invasive cancer cells (n = 12). While 54% of invasive cancer cells (n = 27) also accumulated PIs-MUFA, 46% of invasive cancer cells (n = 23) accumulated the PIs-PUFA, PI(18:0/20:3) and PI(18:0/20:4). The accumulation of PI(18:0/20:3) was associated with higher incidence of lymph node metastasis and activation of the PD-1-related immune checkpoint pathway. Fatty acid-binding protein 7 was identified as a putative molecule controlling PI composition. CONCLUSIONS: MALDI-IMS identified PI composition associated with invasion and nodal metastasis of breast cancer. The accumulation of PI(18:0/20:3) could affect the PD-1-related immune checkpoint pathway, although its precise mechanism should be further validated. |
format | Online Article Text |
id | pubmed-7051979 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-70519792020-12-10 High-resolution imaging mass spectrometry combined with transcriptomic analysis identified a link between fatty acid composition of phosphatidylinositols and the immune checkpoint pathway at the primary tumour site of breast cancer Kawashima, Masahiro Tokiwa, Mariko Nishimura, Tomomi Kawata, Yukiko Sugimoto, Masahiro Kataoka, Tatsuki R. Sakurai, Takaki Iwaisako, Keiko Suzuki, Eiji Hagiwara, Masatoshi Harris, Adrian L. Toi, Masakazu Br J Cancer Article BACKGROUND: The fatty acid (FA) composition of phosphatidylinositols (PIs) is tightly regulated in mammalian tissue since its disruption impairs normal cellular functions. We previously found its significant alteration in breast cancer by using matrix-assisted laser desorption and ionisation imaging mass spectrometry (MALDI-IMS). METHODS: We visualised the histological distribution of PIs containing different FAs in 65 primary breast cancer tissues using MALDI-IMS and investigated its association with clinicopathological features and gene expression profiles. RESULTS: Normal ductal cells (n = 7) predominantly accumulated a PI containing polyunsaturated FA (PI-PUFA), PI(18:0/20:4). PI(18:0/20:4) was replaced by PIs containing monounsaturated FA (PIs-MUFA) in all non-invasive cancer cells (n = 12). While 54% of invasive cancer cells (n = 27) also accumulated PIs-MUFA, 46% of invasive cancer cells (n = 23) accumulated the PIs-PUFA, PI(18:0/20:3) and PI(18:0/20:4). The accumulation of PI(18:0/20:3) was associated with higher incidence of lymph node metastasis and activation of the PD-1-related immune checkpoint pathway. Fatty acid-binding protein 7 was identified as a putative molecule controlling PI composition. CONCLUSIONS: MALDI-IMS identified PI composition associated with invasion and nodal metastasis of breast cancer. The accumulation of PI(18:0/20:3) could affect the PD-1-related immune checkpoint pathway, although its precise mechanism should be further validated. Nature Publishing Group UK 2019-12-10 2020-01-21 /pmc/articles/PMC7051979/ /pubmed/31819188 http://dx.doi.org/10.1038/s41416-019-0662-8 Text en © The Author(s), under exclusive licence to Cancer Research UK 2019 https://creativecommons.org/licenses/by/4.0/Note: This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0). |
spellingShingle | Article Kawashima, Masahiro Tokiwa, Mariko Nishimura, Tomomi Kawata, Yukiko Sugimoto, Masahiro Kataoka, Tatsuki R. Sakurai, Takaki Iwaisako, Keiko Suzuki, Eiji Hagiwara, Masatoshi Harris, Adrian L. Toi, Masakazu High-resolution imaging mass spectrometry combined with transcriptomic analysis identified a link between fatty acid composition of phosphatidylinositols and the immune checkpoint pathway at the primary tumour site of breast cancer |
title | High-resolution imaging mass spectrometry combined with transcriptomic analysis identified a link between fatty acid composition of phosphatidylinositols and the immune checkpoint pathway at the primary tumour site of breast cancer |
title_full | High-resolution imaging mass spectrometry combined with transcriptomic analysis identified a link between fatty acid composition of phosphatidylinositols and the immune checkpoint pathway at the primary tumour site of breast cancer |
title_fullStr | High-resolution imaging mass spectrometry combined with transcriptomic analysis identified a link between fatty acid composition of phosphatidylinositols and the immune checkpoint pathway at the primary tumour site of breast cancer |
title_full_unstemmed | High-resolution imaging mass spectrometry combined with transcriptomic analysis identified a link between fatty acid composition of phosphatidylinositols and the immune checkpoint pathway at the primary tumour site of breast cancer |
title_short | High-resolution imaging mass spectrometry combined with transcriptomic analysis identified a link between fatty acid composition of phosphatidylinositols and the immune checkpoint pathway at the primary tumour site of breast cancer |
title_sort | high-resolution imaging mass spectrometry combined with transcriptomic analysis identified a link between fatty acid composition of phosphatidylinositols and the immune checkpoint pathway at the primary tumour site of breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051979/ https://www.ncbi.nlm.nih.gov/pubmed/31819188 http://dx.doi.org/10.1038/s41416-019-0662-8 |
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