Identification of Metastasis-Associated Metabolic Profiles of Tumors by 1H-HR-MAS-MRS

Tumors develop an abnormal microenvironment during growth, and similar to the metastatic phenotype, the metabolic phenotype of cancer cells is tightly linked to characteristics of the tumor microenvironment (TME). In this study, we explored relationships between metabolic profile, metastatic propens...

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Main Authors: Saurabh S. Gorad, Christine Ellingsen, Tone F. Bathen, Berit S. Mathiesen, Siver A. Moestue, Einar K. Rofstad
Format: Article
Language:English
Published: Elsevier 2015-10-01
Series:Neoplasia: An International Journal for Oncology Research
Online Access:http://www.sciencedirect.com/science/article/pii/S147655861500127X
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author Saurabh S. Gorad
Christine Ellingsen
Tone F. Bathen
Berit S. Mathiesen
Siver A. Moestue
Einar K. Rofstad
author_facet Saurabh S. Gorad
Christine Ellingsen
Tone F. Bathen
Berit S. Mathiesen
Siver A. Moestue
Einar K. Rofstad
author_sort Saurabh S. Gorad
collection DOAJ
description Tumors develop an abnormal microenvironment during growth, and similar to the metastatic phenotype, the metabolic phenotype of cancer cells is tightly linked to characteristics of the tumor microenvironment (TME). In this study, we explored relationships between metabolic profile, metastatic propensity, and hypoxia in experimental tumors in an attempt to identify metastasis-associated metabolic profiles. Two human melanoma xenograft lines (A-07, R-18) showing different TMEs were used as cancer models. Metabolic profile was assessed by proton high resolution magic angle spinning magnetic resonance spectroscopy (1H-HR-MAS-MRS). Tumor hypoxia was detected in immunostained histological preparations by using pimonidazole as a hypoxia marker. Twenty-four samples from 10 A-07 tumors and 28 samples from 10 R-18 tumors were analyzed. Metastasis was associated with hypoxia in both A-07 and R-18 tumors, and 1H-HR-MAS-MRS discriminated between tissue samples with and tissue samples without hypoxic regions in both models, primarily because hypoxia was associated with high lactate resonance peaks in A-07 tumors and with low lactate resonance peaks in R-18 tumors. Similarly, metastatic and non-metastatic R-18 tumors showed significantly different metabolic profiles, but not metastatic and non-metastatic A-07 tumors, probably because some samples from the metastatic A-07 tumors were derived from tumor regions without hypoxic tissue. This study suggests that 1H-HR-MAS-MRS may be a valuable tool for evaluating the role of hypoxia and lactate in tumor metastasis as well as for identification of metastasis-associated metabolic profiles.
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spelling doaj.art-733a953f427a4982895a3a540f61d6762022-12-21T17:32:23ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022015-10-01171076777510.1016/j.neo.2015.10.001Identification of Metastasis-Associated Metabolic Profiles of Tumors by 1H-HR-MAS-MRSSaurabh S. Gorad0Christine Ellingsen1Tone F. Bathen2Berit S. Mathiesen3Siver A. Moestue4Einar K. Rofstad5Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, NorwayDepartment of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, NorwayDepartment of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, NorwayDepartment of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, NorwayDepartment of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, NorwayDepartment of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, NorwayTumors develop an abnormal microenvironment during growth, and similar to the metastatic phenotype, the metabolic phenotype of cancer cells is tightly linked to characteristics of the tumor microenvironment (TME). In this study, we explored relationships between metabolic profile, metastatic propensity, and hypoxia in experimental tumors in an attempt to identify metastasis-associated metabolic profiles. Two human melanoma xenograft lines (A-07, R-18) showing different TMEs were used as cancer models. Metabolic profile was assessed by proton high resolution magic angle spinning magnetic resonance spectroscopy (1H-HR-MAS-MRS). Tumor hypoxia was detected in immunostained histological preparations by using pimonidazole as a hypoxia marker. Twenty-four samples from 10 A-07 tumors and 28 samples from 10 R-18 tumors were analyzed. Metastasis was associated with hypoxia in both A-07 and R-18 tumors, and 1H-HR-MAS-MRS discriminated between tissue samples with and tissue samples without hypoxic regions in both models, primarily because hypoxia was associated with high lactate resonance peaks in A-07 tumors and with low lactate resonance peaks in R-18 tumors. Similarly, metastatic and non-metastatic R-18 tumors showed significantly different metabolic profiles, but not metastatic and non-metastatic A-07 tumors, probably because some samples from the metastatic A-07 tumors were derived from tumor regions without hypoxic tissue. This study suggests that 1H-HR-MAS-MRS may be a valuable tool for evaluating the role of hypoxia and lactate in tumor metastasis as well as for identification of metastasis-associated metabolic profiles.http://www.sciencedirect.com/science/article/pii/S147655861500127X
spellingShingle Saurabh S. Gorad
Christine Ellingsen
Tone F. Bathen
Berit S. Mathiesen
Siver A. Moestue
Einar K. Rofstad
Identification of Metastasis-Associated Metabolic Profiles of Tumors by 1H-HR-MAS-MRS
Neoplasia: An International Journal for Oncology Research
title Identification of Metastasis-Associated Metabolic Profiles of Tumors by 1H-HR-MAS-MRS
title_full Identification of Metastasis-Associated Metabolic Profiles of Tumors by 1H-HR-MAS-MRS
title_fullStr Identification of Metastasis-Associated Metabolic Profiles of Tumors by 1H-HR-MAS-MRS
title_full_unstemmed Identification of Metastasis-Associated Metabolic Profiles of Tumors by 1H-HR-MAS-MRS
title_short Identification of Metastasis-Associated Metabolic Profiles of Tumors by 1H-HR-MAS-MRS
title_sort identification of metastasis associated metabolic profiles of tumors by 1h hr mas mrs
url http://www.sciencedirect.com/science/article/pii/S147655861500127X
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