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Genetic deletion of receptor for hyaluronan-mediated motility (Rhamm) attenuates the formation of aggressive fibromatosis (desmoid tumor).

Publication ,  Journal Article
Tolg, C; Poon, R; Fodde, R; Turley, EA; Alman, BA
Published in: Oncogene
October 9, 2003

Aggressive fibromatosis (desmoid tumor) is a locally invasive soft tissue neoplasm associated with mutations resulting in beta-catenin-mediated transcriptional activation. This tumor is composed of cells with histological and molecular characteristics common to proliferating mesenchymal cells of dermal wounds. Using immunohistochemistry and RT-PCR, we show that Rhamm, a protein with an important role in wound healing and neoplastic progression, is also expressed at high levels in aggressive fibromatosis. A mouse harboring a targeted deletion in Rhamm was generated, resulting in viable Rhamm-/- animals. Rhamm-/- mice were crossed with Apc/Apc1638N mice, which harbor a targeted mutation in the Apc gene predisposing animals to gastrointestinal and aggressive fibromatosis tumors. Rhamm deficiency significantly decreased the number of aggressive fibromatosis tumors formed, but did not alter the number of gastrointestinal polyps. Cell culture studies show that Rhamm regulates cell proliferation in both fibroblasts and fibromatosis cells under conditions of low density, but not high density. These results suggest that Rhamm regulates proliferation of cells with sparse cell-cell contacts, such as occurs in aggressive fibromatosis; provides the first genetic evidence implicating Rhamm in tumor pathology; and suggest Rhamm blockade as a potential therapeutic target for this otherwise difficult-to-treat neoplasm.

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Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

October 9, 2003

Volume

22

Issue

44

Start / End Page

6873 / 6882

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Oncology & Carcinogenesis
  • Mice, Transgenic
  • Mice, Knockout
  • Mice
  • Hyaluronan Receptors
  • Genetic Predisposition to Disease
  • Genes, APC
  • Gene Targeting
  • Gene Expression Regulation, Neoplastic
 

Citation

APA
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ICMJE
MLA
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Tolg, C., Poon, R., Fodde, R., Turley, E. A., & Alman, B. A. (2003). Genetic deletion of receptor for hyaluronan-mediated motility (Rhamm) attenuates the formation of aggressive fibromatosis (desmoid tumor). Oncogene, 22(44), 6873–6882. https://doi.org/10.1038/sj.onc.1206811
Tolg, Cornelia, Raymoond Poon, Riccardo Fodde, Eva Ann Turley, and Benjamin Aaron Alman. “Genetic deletion of receptor for hyaluronan-mediated motility (Rhamm) attenuates the formation of aggressive fibromatosis (desmoid tumor).Oncogene 22, no. 44 (October 9, 2003): 6873–82. https://doi.org/10.1038/sj.onc.1206811.
Tolg, Cornelia, et al. “Genetic deletion of receptor for hyaluronan-mediated motility (Rhamm) attenuates the formation of aggressive fibromatosis (desmoid tumor).Oncogene, vol. 22, no. 44, Oct. 2003, pp. 6873–82. Pubmed, doi:10.1038/sj.onc.1206811.

Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

October 9, 2003

Volume

22

Issue

44

Start / End Page

6873 / 6882

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Oncology & Carcinogenesis
  • Mice, Transgenic
  • Mice, Knockout
  • Mice
  • Hyaluronan Receptors
  • Genetic Predisposition to Disease
  • Genes, APC
  • Gene Targeting
  • Gene Expression Regulation, Neoplastic