Polyploid Giant Cancer Cells Actuate Prostate Cancer Tumor Resistance and Lethal Phenotype
Abstract
Lethal prostate cancer is incurable because the population of cancer cells within a tumor are resistant to all known compounds, including standard-of care therapy. Resistance to a therapy may be solely cell intrinsic, therefore present in a treatment-nave setting, as well as be induced through external selective pressure via therapeutic treatment. How and when drug resistance arises has profound implications to understand tumorigenesis as well as to guide treatment and management of disease. We and others have have demonstrated that the appearance of a subset of morphologically distinct cancer cells with high genomic content, polyploid giant cancer cells (PGCCs), is associated with therapeutic interventions. Based on our preliminary results, we hypothesize that PGCCs are central mediators of tumor resistance and prostate cancer lethality. To test this hypothesis, we will: 1) determine how and when PGCCs are formed during cancer progression and 2) demonstrate that quiescence underlies a common mechanism of stress resistance in PGCCs. The results of the above studies will fundamentally change our understanding of how and when therapeutic resistance arises during prostate tumorigenesis and its treatment course, specifically delineating the role of polyploid giant cancer cells as mediators of therapeutic resistance in prostate tumors. In the current term, we have begun to understand the mechanisms of PGCC formation resulting in a single nucleus or multiple nuclei. We haves own that PGCCs arise under multiple tumor microenvironmental stressors, including hypoxia and altered pH. We found that PGCCs under therapy exist in a G0 quiescent state. Finally, we have demonstrated that PGCCs have stem like properties, both in terms of function and molecular markers. This work has resulted in multiple peer-reviewed publications in the last year.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2023
- Accession Number
- AD1206372
Entities
People
- Sarah R Amend
Organizations
- Johns Hopkins University
- University of Maryland, Baltimore
- University of Michigan