HYALURONAN BIOSYNTHESIS IN PROSTATE CARCINOMA

  • Simpson, Melanie A, (PI)

Project: Research project

Description

Prostate cancer morbidity is the second leading cause of cancer death in the United States, generally resulting from metastases in remote sites, and is one of a few major cancers that preferentially invade bone marrow. Previous work in our laboratory demonstrated that avid adhesion of prostate tumor cells to bone marrow endothelial cells was mediated by a prostate cell surface hyaluronan (HA) matrix. The presence of this high molecular weight glycosaminoglycan in elevated quantities is correlated with normal and transformed cell migration. Its synthesis is catalyzed by one or more of three HA synthase (HAS) isoforms in humans. We hypothesize that the ability of the prostate tumor cell to synthesize an HA coat will be isoform specific and correlate with invasive phenotype in vitro and in mouse models. We propose to test this model by characterizing the requirement of an HA coat for in vitro correlate assays of aggressive tumor behavior, with respect to HAS isoform expression and metastatic propensity. We will assess the functional relevance of each HAS isoform to prostate tumor malignancy using prostate carcinomas stably transfected with antisense or full length overexpression HAS constructs to measure invasiveness following specific alteration of HAS expression levels, both in vitro and in a prostate-injected mouse model.
StatusActive
Effective start/end date4/1/00 → …

Funding

  • National Institutes of Health: $37,516.00
  • National Institutes of Health: $41,996.00
  • National Institutes of Health: $18,618.00

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Hyaluronic Acid
Prostate
Carcinoma
Protein Isoforms
Neoplasms
Aptitude
Glycosaminoglycans
Bone Marrow Cells
Cell Movement
Cause of Death
Prostatic Neoplasms
Endothelial Cells
Molecular Weight
Bone Marrow
Neoplasm Metastasis
Morbidity
Phenotype
In Vitro Techniques

ASJC

  • Medicine(all)