Lactate in Sarcoma Microenvironment: Much More than just a Waste Product
Sarcomas are rare and heterogeneous malignant tumors relatively resistant to radio- and chemotherapy. Sarcoma progression is deeply dependent on environmental conditions that sustain both cancer growth and invasive abilities. Sarcoma microenvironment is composed of different stromal cell types and e...
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doaj-2335aaaf74de4e01bc9e93a29fd69c642020-11-25T02:16:11ZengMDPI AGCells2073-44092020-02-019251010.3390/cells9020510cells9020510Lactate in Sarcoma Microenvironment: Much More than just a Waste ProductMaria Letizia Taddei0Laura Pietrovito1Angela Leo2Paola Chiarugi3Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Viale Morgagni 50, 50142 Firenze, ItalyDipartimento di Scienze Biomediche Sperimentali e Cliniche, Università degli Studi di Firenze, Viale Morgagni 50, 50142 Firenze, ItalyDipartimento di Scienze Biomediche Sperimentali e Cliniche, Università degli Studi di Firenze, Viale Morgagni 50, 50142 Firenze, ItalyDipartimento di Scienze Biomediche Sperimentali e Cliniche, Università degli Studi di Firenze, Viale Morgagni 50, 50142 Firenze, ItalySarcomas are rare and heterogeneous malignant tumors relatively resistant to radio- and chemotherapy. Sarcoma progression is deeply dependent on environmental conditions that sustain both cancer growth and invasive abilities. Sarcoma microenvironment is composed of different stromal cell types and extracellular proteins. In this context, cancer cells may cooperate or compete with stromal cells for metabolic nutrients to sustain their survival and to adapt to environmental changes. The strict interplay between stromal and sarcoma cells deeply affects the extracellular metabolic milieu, thus altering the behavior of both cancer cells and other non-tumor cells, including immune cells. Cancer cells are typically dependent on glucose fermentation for growth and lactate is one of the most heavily increased metabolites in the tumor bulk. Currently, lactate is no longer considered a waste product of the Warburg metabolism, but novel signaling molecules able to regulate the behavior of tumor cells, tumor-stroma interactions and the immune response. In this review, we illustrate the role of lactate in the strong acidity microenvironment of sarcoma. Really, in the biological context of sarcoma, where novel targeted therapies are needed to improve patient outcomes in combination with current therapies or as an alternative treatment, lactate targeting could be a promising approach to future clinical trials.https://www.mdpi.com/2073-4409/9/2/510sarcomalactatemicroenvironmentacidityimmune response |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maria Letizia Taddei Laura Pietrovito Angela Leo Paola Chiarugi |
spellingShingle |
Maria Letizia Taddei Laura Pietrovito Angela Leo Paola Chiarugi Lactate in Sarcoma Microenvironment: Much More than just a Waste Product Cells sarcoma lactate microenvironment acidity immune response |
author_facet |
Maria Letizia Taddei Laura Pietrovito Angela Leo Paola Chiarugi |
author_sort |
Maria Letizia Taddei |
title |
Lactate in Sarcoma Microenvironment: Much More than just a Waste Product |
title_short |
Lactate in Sarcoma Microenvironment: Much More than just a Waste Product |
title_full |
Lactate in Sarcoma Microenvironment: Much More than just a Waste Product |
title_fullStr |
Lactate in Sarcoma Microenvironment: Much More than just a Waste Product |
title_full_unstemmed |
Lactate in Sarcoma Microenvironment: Much More than just a Waste Product |
title_sort |
lactate in sarcoma microenvironment: much more than just a waste product |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2020-02-01 |
description |
Sarcomas are rare and heterogeneous malignant tumors relatively resistant to radio- and chemotherapy. Sarcoma progression is deeply dependent on environmental conditions that sustain both cancer growth and invasive abilities. Sarcoma microenvironment is composed of different stromal cell types and extracellular proteins. In this context, cancer cells may cooperate or compete with stromal cells for metabolic nutrients to sustain their survival and to adapt to environmental changes. The strict interplay between stromal and sarcoma cells deeply affects the extracellular metabolic milieu, thus altering the behavior of both cancer cells and other non-tumor cells, including immune cells. Cancer cells are typically dependent on glucose fermentation for growth and lactate is one of the most heavily increased metabolites in the tumor bulk. Currently, lactate is no longer considered a waste product of the Warburg metabolism, but novel signaling molecules able to regulate the behavior of tumor cells, tumor-stroma interactions and the immune response. In this review, we illustrate the role of lactate in the strong acidity microenvironment of sarcoma. Really, in the biological context of sarcoma, where novel targeted therapies are needed to improve patient outcomes in combination with current therapies or as an alternative treatment, lactate targeting could be a promising approach to future clinical trials. |
topic |
sarcoma lactate microenvironment acidity immune response |
url |
https://www.mdpi.com/2073-4409/9/2/510 |
work_keys_str_mv |
AT marialetiziataddei lactateinsarcomamicroenvironmentmuchmorethanjustawasteproduct AT laurapietrovito lactateinsarcomamicroenvironmentmuchmorethanjustawasteproduct AT angelaleo lactateinsarcomamicroenvironmentmuchmorethanjustawasteproduct AT paolachiarugi lactateinsarcomamicroenvironmentmuchmorethanjustawasteproduct |
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