Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
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
_version_ 1783502772353630208
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
work_keys_str_mv AT kawashimamasahiro highresolutionimagingmassspectrometrycombinedwithtranscriptomicanalysisidentifiedalinkbetweenfattyacidcompositionofphosphatidylinositolsandtheimmunecheckpointpathwayattheprimarytumoursiteofbreastcancer
AT tokiwamariko highresolutionimagingmassspectrometrycombinedwithtranscriptomicanalysisidentifiedalinkbetweenfattyacidcompositionofphosphatidylinositolsandtheimmunecheckpointpathwayattheprimarytumoursiteofbreastcancer
AT nishimuratomomi highresolutionimagingmassspectrometrycombinedwithtranscriptomicanalysisidentifiedalinkbetweenfattyacidcompositionofphosphatidylinositolsandtheimmunecheckpointpathwayattheprimarytumoursiteofbreastcancer
AT kawatayukiko highresolutionimagingmassspectrometrycombinedwithtranscriptomicanalysisidentifiedalinkbetweenfattyacidcompositionofphosphatidylinositolsandtheimmunecheckpointpathwayattheprimarytumoursiteofbreastcancer
AT sugimotomasahiro highresolutionimagingmassspectrometrycombinedwithtranscriptomicanalysisidentifiedalinkbetweenfattyacidcompositionofphosphatidylinositolsandtheimmunecheckpointpathwayattheprimarytumoursiteofbreastcancer
AT kataokatatsukir highresolutionimagingmassspectrometrycombinedwithtranscriptomicanalysisidentifiedalinkbetweenfattyacidcompositionofphosphatidylinositolsandtheimmunecheckpointpathwayattheprimarytumoursiteofbreastcancer
AT sakuraitakaki highresolutionimagingmassspectrometrycombinedwithtranscriptomicanalysisidentifiedalinkbetweenfattyacidcompositionofphosphatidylinositolsandtheimmunecheckpointpathwayattheprimarytumoursiteofbreastcancer
AT iwaisakokeiko highresolutionimagingmassspectrometrycombinedwithtranscriptomicanalysisidentifiedalinkbetweenfattyacidcompositionofphosphatidylinositolsandtheimmunecheckpointpathwayattheprimarytumoursiteofbreastcancer
AT suzukieiji highresolutionimagingmassspectrometrycombinedwithtranscriptomicanalysisidentifiedalinkbetweenfattyacidcompositionofphosphatidylinositolsandtheimmunecheckpointpathwayattheprimarytumoursiteofbreastcancer
AT hagiwaramasatoshi highresolutionimagingmassspectrometrycombinedwithtranscriptomicanalysisidentifiedalinkbetweenfattyacidcompositionofphosphatidylinositolsandtheimmunecheckpointpathwayattheprimarytumoursiteofbreastcancer
AT harrisadrianl highresolutionimagingmassspectrometrycombinedwithtranscriptomicanalysisidentifiedalinkbetweenfattyacidcompositionofphosphatidylinositolsandtheimmunecheckpointpathwayattheprimarytumoursiteofbreastcancer
AT toimasakazu highresolutionimagingmassspectrometrycombinedwithtranscriptomicanalysisidentifiedalinkbetweenfattyacidcompositionofphosphatidylinositolsandtheimmunecheckpointpathwayattheprimarytumoursiteofbreastcancer