| Start Date: | 6/15/2016 | Start Time: | 3:00 PM |
| End Date: | 6/15/2016 | End Time: | 5:00 PM |
|
Event Description
BIOMED PhD Research Proposal
Title:
The Role of IL-1β in Early Colonization of Prostate Cancer Cells
Speaker:
Melisa Diaz, PhD Candidate, School of Biomedical Engineering, Science and Health Systems
Advisors:
Amy Throckmorton, PhD, Associate Professor, School of Biomedical Engineering, Science and Health Systems
Alessandro Fatatis, MD, PhD, Professor, Department of Pharmacology and Physiology, Drexel University College of Medicine
Abstract:
Prostate cancer (PCa) is the most common cancer in men in the United States. In the vast majority of patients, death from this tumor occurs when cancerous cells leave the prostate to disseminate and grow in distant organs, in a process called metastasis. The most common site of distant spread is the bone and more than 90% of patients that die from this disease present with secondary bone tumors. PCa is highly dependent on the stimulation of the Androgen Receptor (AR) by testosterone. Thus, current standards of care target AR activation and signaling and consistently reduce tumor burden, but skeletal metastases remain incurable and represent an unmet clinical need. Cancer cells spreading from primary tumors need to adapt to the tissue microenvironment of targeted organs. This process may involve the conditioning of the newly found stroma starting immediately after the arrival of cancer cells to secondary sites.
Preliminary data has shown that expression of interleukin-1β (IL-1β) promotes metastatic behavior of PCa cells in animal models by conditioning the bone stroma and facilitating colonization and tumor growth in the skeleton. Interestingly, human specimens from skeletal metastatic tumors in prostate cancer patients show a mutually exclusive relationship between IL-1β and AR. Consistently, AR positive (AR+) human PCa cell lines also fail to express IL-1β, whereas the human AR-negative (AR−) PC3-ML cell line expresses high levels of the cytokine. AR− PC3-ML cells are highly metastatic in animal models; in contrast, AR+ cancer cells consistently fail to generate secondary tumors in mice unless they are co-inoculated with PC3-ML cells. Our preliminary data have also shown that IL-1β knockdown significantly impairs the survival and growth of PC3-ML cells at the skeletal level. Finally, we have evidence that IL-1β activates human Mesenchymal Stem Cells (hMSC) in the bone stroma, converting them into Carcinoma Associated Fibroblasts (CAFs) to support tumor growth. |
|
Location:
Bossone Research Center, Room 709, located at 32nd and Market Streets. |
Audience:
Undergraduate StudentsGraduate StudentsFacultyStaff |
|
