cd44 deletion suppresses atypia in the precancerous mouse testis

Mol Carcinog. 2019 May;58(5):621-626. doi: 10.1002/mc.22961. Epub 2019 Jan 28.


Loss-of-function of RHAMM causes hypofertility and testicular atrophy in young mice, followed by germ cell neoplasia in situ (GCNIS) of the testis, cellular atypia, and development of the testicular germ cell tumor (TGCT) seminoma. These pathologies reflect the risk factors and phenotypes that precede seminoma development in humans and-given the high prevalence of RHAMM downregulation in human seminoma-link RHAMM dysfunction with the aetiology of male hypofertility and GCNIS-related TGCTs. The initiating event underlying these pathologies, in RHAMM mutant testis, is premature displacement of undifferentiated progenitors from the basal compartment. We hypothesized that cd44 (both cancer initiating cell- and oncogenic progression marker) will drive GCNIS development, induced by RHAMM-loss-of-function in the mouse. We report that cd44 is expressed in a specific subset of GCNIS testes. Its genetic deletion has no effect on GCNIS onset, but it ameliorates oncogenic progression. We conclude that cd44 expression, combined with RHAMM dysfunction, promotes oncogenic progression in the testis.

Keywords: CD44; RHAMM; germ cell neoplasia in situ; testicular atypia; testicular germ cell tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics
  • Carcinoma in Situ / genetics
  • Carcinoma in Situ / metabolism
  • Carcinoma in Situ / prevention & control*
  • Extracellular Matrix Proteins / physiology*
  • Female
  • Hyaluronan Receptors / physiology*
  • Infertility, Male / genetics
  • Infertility, Male / metabolism
  • Infertility, Male / prevention & control*
  • Male
  • Mice
  • Mice, Transgenic
  • Neoplasms, Germ Cell and Embryonal / genetics
  • Neoplasms, Germ Cell and Embryonal / metabolism
  • Neoplasms, Germ Cell and Embryonal / prevention & control*
  • Precancerous Conditions / genetics
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / prevention & control*
  • Sequence Deletion
  • Testicular Neoplasms / genetics
  • Testicular Neoplasms / metabolism
  • Testicular Neoplasms / prevention & control*


  • Biomarkers, Tumor
  • Cd44 protein, mouse
  • Extracellular Matrix Proteins
  • Hyaluronan Receptors
  • hyaluronan-mediated motility receptor

Supplementary concepts

  • Testicular Germ Cell Tumor