Targeting Prostate Cancer Stemlike Cells through Cell Surface-Expressed GRP78
Abstract
In our previous funding period, we showed that prostate cancer cells surviving short term chemotherapy in vitro express increased levels of cell surface GRP78. Based on our hypothesis that cancer stem-like cells express cell surface GRP78, in the current funding period, we tested if chemotherapy-enriched prostate cancer cells exhibit increased sphere forming ability compared to untreated cells. Results indicated that these chemoresidual cells do not show increased spherogenicity, a hallmark of cancer stem-like cells. Accordingly, we shifted our attention to sorting cell surface GRP78-positive and cell surface GRP78-negative prostate cancer cells and determining their relative sphere forming ability. In fact, we observed increased spherogenicity of cell surface GRP78-positive prostate cancer stem-like cells, thus addressing the hypothesis that cell surface GRP78 drives cancer stem-like cell behavior. We then tested effects of a GRP78 carboxy terminal(C-terminal) antibody on sphere forming ability of these sorted GRP78-positive cells. This GRP78 antibody abolished sphere formation by these cells. This data demonstrates efficacy of targeting cell surface GRP78 to reduce cancer stem-like cell behavior. In the previous grant cycle, we had a company generate new Cterminal GRP78 antibodies in mice. In the current cycle, we requested expansion/purification of two of the GRP78 antibodies that showed cell surface staining of prostate cancer cells. In the next grant funding cycle, we will compare the relative abilities of these new antibodies (and our previously studied C-terminal GRP78 antibody, C38) to inhibit sphere growth of GRP78-sorted prostate cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2014
- Accession Number
- ADA613546
Entities
People
- Robin E. Bachelder
- Salvatore Pizzo
Organizations
- Duke University