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Esophageal Cancer Development: Crucial Clues Arising from the Extracellular Matrix

1
Laboratório de Interações Celulares, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro Prédio de Ciências da Saúde—Cidade Universitária, Ilha do Fundão, Av. Carlos Chagas, 373—bloco F, sala 26, Rio de Janeiro CEP: 21941-902, RJ, Brazil
2
Programa de Carcinogênese Molecular, Instituto Nacional de Câncer—INCA, Rua André Cavalcanti, 37—Centro, Rio de Janeiro CEP: 20231-050, RJ, Brazil
3
Laboratório de Pinças Óticas (LPO-COPEA), Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil
4
Laboratório de Proliferação e Diferenciação Celular, Instituto de Ciências Biomédicas (ICB), Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil
*
Author to whom correspondence should be addressed.
Cells 2020, 9(2), 455; https://doi.org/10.3390/cells9020455
Received: 30 December 2019 / Revised: 5 February 2020 / Accepted: 13 February 2020 / Published: 17 February 2020
(This article belongs to the Special Issue Micro- and Macro-Environmental Factors in Solid Cancers)
In the last years, the extracellular matrix (ECM) has been reported as playing a relevant role in esophageal cancer (EC) development, with this compartment being related to several aspects of EC genesis and progression. This sounds very interesting due to the complexity of this highly incident and lethal tumor, which takes the sixth position in mortality among all tumor types worldwide. The well-established increase in ECM stiffness, which is able to trigger mechanotransduction signaling, is capable of regulating several malignant behaviors by converting alteration in ECM mechanics into cytoplasmatic biochemical signals. In this sense, it has been shown that some molecules play a key role in these events, particularly the different collagen isoforms, as well as enzymes related to its turnover, such as lysyl oxidase (LOX) and matrix metalloproteinases (MMPs). In fact, MMPs are not only involved in ECM stiffness, but also in other events related to ECM homeostasis, which includes ECM remodeling. Therefore, the crucial role of distinct MMPs isoform has already been reported, especially MMP-2, -3, -7, and -9, along EC development, thus strongly associating these proteins with the control of important cellular events during tumor progression, particularly in the process of invasion during metastasis establishment. In addition, by distinct mechanisms, a vast diversity of glycoproteins and proteoglycans, such as laminin, fibronectin, tenascin C, galectin, dermatan sulfate, and hyaluronic acid exert remarkable effects in esophageal malignant cells due to the activation of oncogenic signaling pathways mainly involved in cytoskeleton alterations during adhesion and migration processes. Finally, the wide spectrum of interactions potentially mediated by ECM may represent a singular intervention scenario in esophageal carcinogenesis natural history and, due to the scarce knowledge on the cellular and molecular mechanisms involved in EC development, the growing body of evidence on ECM’s role along esophageal carcinogenesis might provide a solid base to improve its management in the future. View Full-Text
Keywords: esophageal carcinogenesis; extracellular matrix; stiffness; remodeling; adhesion; metalloproteinases; glycoproteins; proteoglycans esophageal carcinogenesis; extracellular matrix; stiffness; remodeling; adhesion; metalloproteinases; glycoproteins; proteoglycans
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MDPI and ACS Style

Palumbo, A., Jr.; Meireles Da Costa, N.; Pontes, B.; Leite de Oliveira, F.; Lohan Codeço, M.; Ribeiro Pinto, L.F.; Nasciutti, L.E. Esophageal Cancer Development: Crucial Clues Arising from the Extracellular Matrix. Cells 2020, 9, 455. https://doi.org/10.3390/cells9020455

AMA Style

Palumbo A Jr., Meireles Da Costa N, Pontes B, Leite de Oliveira F, Lohan Codeço M, Ribeiro Pinto LF, Nasciutti LE. Esophageal Cancer Development: Crucial Clues Arising from the Extracellular Matrix. Cells. 2020; 9(2):455. https://doi.org/10.3390/cells9020455

Chicago/Turabian Style

Palumbo, Antonio, Jr.; Meireles Da Costa, Nathalia; Pontes, Bruno; Leite de Oliveira, Felipe; Lohan Codeço, Matheus; Ribeiro Pinto, Luis F.; Nasciutti, Luiz E. 2020. "Esophageal Cancer Development: Crucial Clues Arising from the Extracellular Matrix" Cells 9, no. 2: 455. https://doi.org/10.3390/cells9020455

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