Esophageal Cancer Development: Crucial Clues Arising from the Extracellular Matrix
Open Access
- 17 February 2020
- Vol. 9 (2), 455
- https://doi.org/10.3390/cells9020455
Abstract
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.Keywords
This publication has 163 references indexed in Scilit:
- The potential of molecular markers to improve interventions through the natural history of oesophageal squamous cell carcinomaBioscience Reports, 2013
- The extracellular matrix: A dynamic niche in cancer progressionThe Journal of cell biology, 2012
- Collagen I Induces Discoidin Domain Receptor (DDR) 1 Expression through DDR2 and a JAK2-ERK1/2-mediated Mechanism in Primary Human Lung FibroblastsPublished by Elsevier BV ,2011
- Hallmarks of Cancer: The Next GenerationCell, 2011
- Hyaluronan Stabilizes Focal Adhesions, Filopodia, and the Proliferative Phenotype in Esophageal Squamous Carcinoma CellsPublished by Elsevier BV ,2010
- Bidirectional extracellular matrix signaling during tissue morphogenesisCytokine & Growth Factor Reviews, 2009
- Clinical significance of LAMB3 and COL7A1 mRNA in esophageal squamous cell carcinomaEuropean Journal of Surgical Oncology, 2009
- Extracellular matrix control of mammary gland morphogenesis and tumorigenesis: insights from imagingHistochemistry and Cell Biology, 2008
- Laminin-332 promotes the invasion of oesophageal squamous cell carcinoma via PI3K activationBritish Journal of Cancer, 2008
- Fibroblasts in cancerNature Reviews Cancer, 2006