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Role of Extracellular Matrix in Gastrointestinal Cancer-Associated Angiogenesis
Eva Andreuzzi1, Alessandra Capuano1, Evelina Poletto1
1Department of Research and Diagnosis, Division of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy.
Abstract:
Gastrointestinal tumors are responsible for more cancer-related fatalities than any other type of tumors, and colorectal and gastric malignancies account for a large part of these diseases. Thus, there is an urgent need to develop new therapeutic approaches to improve the patients' outcome and the tumor microenvironment is a promising arena for the development of such treatments. In fact, the nature of the microenvironment in the different gastrointestinal tracts may significantly influence not only tumor development but also the therapy response. In particular, an important microenvironmental component and a potential therapeutic target is the vasculature. In this context, the extracellular matrix is a key component exerting an active effect in all the hallmarks of cancer, including angiogenesis. Here, we summarized the current knowledge on the role of extracellular matrix in affecting endothelial cell function and intratumoral vascularization in the context of colorectal and gastric cancer. The extracellular matrix acts both directly on endothelial cells and indirectly through its remodeling and the consequent release of growth factors. We envision that a deeper understanding of the role of extracellular matrix and of its remodeling during cancer progression is of chief importance for the development of new, more efficacious, targeted therapies.
Insights
The extracellular matrix influences gastrointestinal tumor growth and therapy response by affecting blood vessel formation. Understanding its role is key to developing new cancer treatments.
Area of Science:
- Oncology
- Cancer Biology
- Gastroenterology
Background:
- Gastrointestinal tumors, particularly colorectal and gastric cancers, are leading causes of cancer mortality.
- The tumor microenvironment significantly impacts tumor progression and therapeutic efficacy.
- Targeting the tumor microenvironment, especially its vasculature, offers promising therapeutic strategies.
Purpose of the Study:
- To summarize current knowledge on the extracellular matrix's role in endothelial cell function and intratumoral vascularization.
- To highlight the extracellular matrix as a potential therapeutic target in gastrointestinal cancers.
- To emphasize the importance of understanding extracellular matrix remodeling in cancer progression.
Main Methods:
- Literature review and synthesis of existing research.
- Analysis of the extracellular matrix's direct and indirect effects on endothelial cells.
- Examination of extracellular matrix remodeling in the context of colorectal and gastric cancer.
Main Results:
- The extracellular matrix actively influences cancer hallmarks, including angiogenesis.
- It affects endothelial cell function directly and indirectly through remodeling and growth factor release.
- Extracellular matrix remodeling plays a critical role in shaping the intratumoral vasculature.
Conclusions:
- The extracellular matrix is a crucial component of the tumor microenvironment in gastrointestinal cancers.
- Its modulation of endothelial cells and vascularization impacts tumor development and treatment response.
- Further understanding of extracellular matrix dynamics is essential for developing novel, targeted cancer therapies.
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