The DOI matches its Crossref record; 270 of the 271 references it cites were found in a registry or an index.
Mechanisms of normal and tumor-derived angiogenesis
Abstract
Often those diseases most evasive to therapeutic intervention usurp the human body's own cellular machinery or deregulate normal physiological processes for propagation. Tumor-induced angiogenesis is a pathological condition that results from aberrant deployment of normal angiogenesis, an essential process in which the vascular tree is remodeled by the growth of new capillaries from preexisting vessels. Normal angiogenesis ensures that developing or healing tissues receive an adequate supply of nutrients. Within the confines of a tumor, the availability of nutrients is limited by competition among actively proliferating cells, and diffusion of metabolites is impeded by high interstitial pressure (Jain RK. Cancer Res 47: 3039–3051, 1987). As a result, tumor cells induce the formation of a new blood supply from the preexisting vasculature, and this affords tumor cells the ability to survive and propagate in a hostile environment. Because both normal and tumor-induced neovascularization fulfill the essential role of satisfying the metabolic demands of a tissue, the mechanisms by which cancer cells stimulate pathological neovascularization mimic those utilized by normal cells to foster physiological angiogenesis. This review investigates mechanisms of tumor-induced angiogenesis. The strategies used by cancer cells to develop their own blood supply are discussed in relation to those employed by normal cells during physiological angiogenesis. With an understanding of blood vessel growth in both normal and abnormal settings, we are better suited to design effective therapeutics for cancer.
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“This hypoxic stress acts as a potent inducer of angiogenic signaling, upregulating key factors such as vascular endothelial growth factor (VEGF) [51].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [51]
In the citing paper
“As the tumor expands beyond this size, the limited diffusion capacity results in the formation of hypoxic regions, which drive tumor dormancy [50,51].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [51]
In the citing paper
“Instead of triggering angiogenesis, some tumors co-opt existing vasculature and grow along the vessels [53][54][55][56], until the demand for nutrients and oxygen becomes too large and angiogenesis starts again [53,55].”
From Cancer-on-chip models for metastasis: importance of the tumor microenvironment (2024) · cites this paper as [53]
In the citing paper
“its presence is essential for initiation of the angiogenic program (76,77)”
From Adipose tissue remodeling and obesity (2011) · cites this paper as [76]
In the citing paper
“VEGF-A is the only bona fide endothelial cell growth factor”
From Adipose tissue remodeling and obesity (2011) · cites this paper as [76]
Citations
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Metadata
- Authors
- Papetti, M., & Herman, I. M.
- Affiliations
- Tufts University (US)
- ORCID
- Herman, Ira M.
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 2002-05-01
- Volume
- 282
- Issue
- 5
- Pages
- C947-C970
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- OpenAlex
- W2050499474
- Cited by
- 809
- References
- 271
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 19 · 2023: 33 · 2022: 38 · 2021: 32 · 2020: 36 · 2019: 28 · 2018: 20 · 2017: 41 · 2016: 36 · 2015: 45 · 2014: 42 · 2013: 46 · 2012: 41
- FWCI
- 2.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Cell Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01gm055110-04)
- National Eye Institute (R01EY009033, EY09033)
- National Institute of General Medical Sciences (GM55110)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK034928)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Physical Sciences › Mathematics › Modeling and Simulation › Mathematical Biology Tumor Growth
- Keywords
- tumor angiogenesis, physiological angiogenesis, tumor blood supply, vascular remodeling, capillary proliferation, interstitial fluid pressure, tumor microenvironment, cancer metabolism
- MeSH terms
- Blood Vessels, Growth Substances, Humans, Models, Cardiovascular, Neoplasms, Neovascularization, Pathologic, Proteins, Receptors, Cell Surface, Neovascularization, Physiologic, Receptor Protein-Tyrosine Kinases, Angiopoietin-2, Receptors, TIE
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