The DOI matches its Crossref record; 88 of the 88 references it cites were found in a registry or an index.
Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis
Open accessAbstract
Expression of HPV16 early region genes in basal keratinocytes of transgenic mice elicits a multistage pathway to squamous carcinoma. We report that infiltration by mast cells and activation of the matrix metalloproteinase MMP-9/gelatinase B coincides with the angiogenic switch in premalignant lesions. Mast cells infiltrate hyperplasias, dysplasias, and invasive fronts of carcinomas, but not the core of solid tumors, where they degranulate in close apposition to capillaries and epithelial basement membranes, releasing mast-cell-specific serine proteases MCP-4 (chymase) and MCP-6 (tryptase). MCP-6 is shown to be a mitogen for dermal fibroblasts that proliferate in the reactive stroma, whereas MCP-4 can activate progelatinase B and induce hyperplastic skin to become angiogenic in an in vitro bioassay. Notably, premalignant angiogenesis is abated in a mast-cell-deficient (KITW/KITWWv) HPV16 transgenic mouse. The data indicate that neoplastic progression in this model involves exploitation of an inflammatory response to tissue abnormality. Thus, regulation of angiogenesis during squamous carcinogenesis is biphasic: In hyperplasias, dysplasias, and invading cancer fronts, inflammatory mast cells are conscripted to reorganize stromal architecture and hyperactivate angiogenesis; within the cancer core, upregulation of angiogenesis factors in tumor cells apparently renders them self-sufficient at sustaining neovascularization.
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“Genetic and functional experiments indicate that neutrophils, mast cells, eosinophils and activated T lymphocytes also contribute to malignancies by releasing extracellular proteases, pro-angiogenic factors and chemokines11,23–26.”
From Inflammation and cancer (2002) · cites this paper as [24]
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Hanahan, D., & Weinberg, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)81683-9 · Cited by 29,219
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Metadata
- Authors
- Coussens, L. M., Raymond, W. W., Bergers, G., Laig-Webster, M., Behrendtsen, O., Werb, Z., Caughey, G. H., & Hanahan, D.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1999-06-01
- Volume
- 13
- Issue
- 11
- Pages
- 1382-1397
- ISSN
- 0890-9369 (ISSN-L)
- PMC
- PMC316772
- OpenAlex
- W2146440075
- Cited by
- 946
- References
- 87
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 11 · 2023: 13 · 2022: 27 · 2021: 18 · 2020: 29 · 2019: 31 · 2018: 27 · 2017: 29 · 2016: 39 · 2015: 32 · 2014: 52 · 2013: 32 · 2012: 49
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL 24136, P01HL024136)
- National Cancer Institute (CA72006, P01CA072006)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- mast cells, angiogenesis, squamous cell carcinoma, HPV16, keratinocytes, MMP-9, chymase, tryptase, precancerous lesions, dermal fibroblasts, tumor stroma, inflammation, carcinogenesis, neovascularization
- MeSH terms
- Animals, Carcinoma, Squamous Cell, Extracellular Matrix, Humans, Mast Cells, Mice, Transgenic, Neovascularization, Pathologic, Serine Endopeptidases, Up-Regulation, Inflammation Mediators, Mice, Tryptases, Chymases
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