Abnormalities of Basement Membrane on Blood Vessels and Endothelial Sprouts in Tumors
Open accessAbstract
Often described as incomplete or absent, the basement membrane of blood vessels in tumors has attracted renewed attention as a source of angiogenic and anti-angiogenic molecules, site of growth factor binding, participant in angiogenesis, and potential target in cancer therapy. This study evaluated the composition, extent, and structural integrity of the basement membrane on blood vessels in three mouse tumor models: spontaneous RIP-Tag2 pancreatic islet tumors, MCa-IV mammary carcinomas, and Lewis lung carcinomas. Tumor vessels were identified by immunohistochemical staining for the endothelial cell markers CD31, endoglin (CD105), vascular endothelial growth factor receptor-2, and integrin alpha5 (CD49e). Confocal microscopic studies revealed that basement membrane identified by type IV collagen immunoreactivity covered >99.9% of the surface of blood vessels in the three tumors, just as in normal pancreatic islets. Laminin, entactin/nidogen, and fibronectin immunoreactivities were similarly ubiquitous on tumor vessels. Holes in the basement membrane, found by analyzing 1- micro m confocal optical sections, were <2.5 micro m in diameter and involved only 0.03% of the vessel surface. Despite the extensive vessel coverage, the basement membrane had conspicuous structural abnormalities, including a loose association with endothelial cells and pericytes, broad extensions away from the vessel wall, and multiple layers visible by electron microscopy. Type IV collagen-immunoreactive sleeves were also present on endothelial sprouts, supporting the idea that basement membrane is present where sprouts grow and regress. These findings indicate that basement membrane covers most tumor vessels but has profound structural abnormalities, consistent with the dynamic nature of endothelial cells and pericytes in tumors.
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Pericytes, along with endothelial cells, are involved in basement membrane remodeling during angiogenesis and tumorigenesis.
“Along with endothelial cells, pericytes are involved in the basement membrane remodeling during angiogenesis [24] and tumorigenesis [25].”
From Tumor microenvironment complexity and therapeutic implications at a glance (2020) · cites this paper as [25]
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- Authors
- Baluk, P., Morikawa, S., Haskell, A., Mancuso, M., & McDonald, D. M.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Morikawa, Shunichi
- McDonald, Donald M.
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2003-11
- Volume
- 163
- Issue
- 5
- Pages
- 1801-1815
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC1892429
- OpenAlex
- W2136596547
- Cited by
- 528
- References
- 57
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 11 · 2023: 25 · 2022: 24 · 2021: 30 · 2020: 29 · 2019: 18 · 2018: 25 · 2017: 33 · 2016: 23 · 2015: 22 · 2014: 26 · 2013: 32 · 2012: 18
- FWCI
- 6.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Massachusetts General Hospital
- National Institutes of Health (HL-59157, HL24136)
- National Heart, Lung, and Blood Institute (R01HL059157, HL 24136, HL 59157, P01HL024136)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- tumor vasculature, angiogenesis, type IV collagen, laminin, fibronectin, pericytes, pancreatic neuroendocrine tumors, breast cancer, Lewis lung carcinoma
- MeSH terms
- Animals, Basement Membrane, Disease Models, Animal, Endothelium, Vascular, Immunohistochemistry, Lung Neoplasms, Male, Mammary Neoplasms, Experimental, Microscopy, Electron, Neovascularization, Pathologic, Pancreatic Neoplasms, Microscopy, Confocal, Mice
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