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Cited by 146Cell Adhesion Molecules ResearchTGF-β signaling in diseasesProtease and Inhibitor Mechanisms

The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.

Antibody-Mediated Blockade of Integrin αvβ6 Inhibits Tumor Progression In vivo by a Transforming Growth Factor-β–Regulated Mechanism

Koopman Van Aarsen, Louise A., Leone, Diane R., Ho, Steffan, Dolinski, Brian M., McCoon, Patricia E., LePage, Doreen J., Kelly, Rebecca, Heaney, Glenna, Rayhorn, Paul, Reid, Carl, Simon, Kenneth J., Horan, Gerald S., Tao, Nianjun, Gardner, Humphrey A., Skelly, Marilyn M., Gown, Allen M., Thomas, Gareth J., Weinreb, Paul H., Fawell, Stephen E., Violette, Shelia M.·2008·Cancer Research
DOI 10.1158/0008-5472.can-07-2307
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Abstract

The αvβ6 integrin is up-regulated on epithelial malignancies and has been implicated in various aspects of cancer progression. Immunohistochemical analysis of αvβ6 expression in 10 human tumor types showed increased expression relative to normal tissues. Squamous carcinomas of the cervix, skin, esophagus, and head and neck exhibited the highest frequency of expression, with positive immunostaining in 92% (n = 46), 84% (n = 49), 68% (n = 56), and 64% (n = 100) of cases, respectively. We studied the role of αvβ6 in Detroit 562 human pharyngeal carcinoma cells in vitro and in vivo. Prominent αvβ6 expression was detected on tumor xenografts at the tumor-stroma interface resembling the expression on human head and neck carcinomas. Nonetheless, coculturing cells in vitro with matrix proteins did not up-regulate αvβ6 expression. Detroit 562 cells showed αvβ6-dependent adhesion and activation of transforming growth factor-β (TGF-β) that was inhibited >90% with an αvβ6 blocking antibody, 6.3G9. Although both recombinant soluble TGF-β receptor type-II (rsTGF-βRII-Fc) and 6.3G9 inhibited TGF-β–mediated Smad2/3 phosphorylation in vitro, there was no effect on proliferation. Conversely, in vivo, 6.3G9 and rsTGF-βRII-Fc inhibited xenograft tumor growth by 50% (n = 10, P < 0.05) and >90% (n = 10, P < 0.001), respectively, suggesting a role for the microenvironment in this response. However, stromal collagen and smooth muscle actin content in xenograft sections were unchanged with treatments. Although further studies are required to consolidate in vitro and in vivo results and define the mechanisms of tumor inhibition by αvβ6 antibodies, our findings support a role for αvβ6 in human cancer and underscore the therapeutic potential of function blocking αvβ6 antibodies. [Cancer Res 2008;68(2):561–70]

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Crossref · 10.1158/0008-5472.can-07-2307

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Metadata

Authors
Koopman Van Aarsen, L. A., Leone, D. R., Ho, S., Dolinski, B. M., McCoon, P. E., LePage, D. J., Kelly, R., Heaney, G., Rayhorn, P., Reid, C., Simon, K. J., Horan, G. S., Tao, N., Gardner, H. A., Skelly, M. M., Gown, A. M., Thomas, G. J., Weinreb, P. H., Fawell, S. E., & Violette, S. M.
Affiliations
  • 1Departments of Discovery Immunology and Discovery Oncology, Biogen Idec, Cambridge, Massachusetts;
  • Biogen (United States) (US)
  • 2Phenopath Laboratories, Seattle, Washington; and
  • Queen Mary University of London (GB)
ORCID
Venue
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2008-01-15
Volume
68
Issue
2
Pages
561-570
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
DOI
10.1158/0008-5472.can-07-2307
OpenAlex
W2106528753
Cited by
146
References
55
Citations by year
2026: 3 · 2025: 11 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 16 · 2020: 8 · 2019: 7 · 2018: 7 · 2017: 8 · 2016: 9 · 2015: 6 · 2014: 13 · 2013: 9 · 2012: 9
FWCI
6.08
Type
journal article
Language
en
Open access
closed
Locations
  • Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
  • ePrints Soton (University of Southampton) (acceptedVersion)
Topics
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Keywords
antibody blocking, TGF-beta, Smad2/3 phosphorylation, tumor progression, pharyngeal cancer, xenograft tumor growth, tumor microenvironment, head and neck squamous cell carcinoma, cell adhesion, tumor-stroma interface
MeSH terms
Receptor, Transforming Growth Factor-beta Type II, Animals, Antibodies, Monoclonal, Carcinoma, Squamous Cell, Cells, Cultured, Female, Humans, Immunoglobulin Fc Fragments, Mice, Nude, Mink, Pharyngeal Neoplasms, Recombinant Fusion Proteins, Signal Transduction, Transforming Growth Factor beta, Protein Serine-Threonine Kinases, Receptors, Transforming Growth Factor beta, Disease Progression, Protein Isoforms, Xenograft Model Antitumor Assays, Integrin alpha5, Cell Proliferation, Mice, Smad Proteins

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