Effects of CD24-RCC2 Signaling on Prostate Cancer Metastasis
Abstract
Prostate cancer is the most common type of cancer in men in the United States. Generally, most prostate tumors are slow-growing and harmless, but some tumors become more aggressive metastatic tumors, which has led to prostate cancer becoming the second leading cause of cancer-related death in American men. Unfortunately, the mechanisms within prostate cells that lead to the dysregulated cell migration and adhesion in tumor metastasis are not fully understood yet. However, research has shown that CD24 is undetected in normal prostates, but expressed in prostate tumors, especially in metastatic tumors, suggesting it may have a role in metastasis. Additionally, recent studies suggested that another gene, RCC2, is responsible for limiting cell motility, including tumor cell metastasis. Importantly, we have found that CD24 can bind RCC2, and CD24 releases the capacity for cell motility as well as cell metastasis in prostate cancer cells. These results suggest that together, these genes control prostate tumor metastasis. Moreover, gene deletion of CD24 in mice blocks prostate tumor progression to metastasis. Based on this novel observation, we hypothesize that CD24, through inhibition of RCC2, induces tumor metastasis in prostate cancer. Our first goal is to determine how CD24-mediated inhibition of RCC2 controls tumor metastasis in prostate cancer animal models. Our preliminary studies in cells have demonstrated that CD24, through inhibition of RCC2, allows the activity of RAC1 and ARF6, which are well known to promote tumor metastasis. Thus, we hypothesize that CD24 accelerates prostate tumor metastasis by allowing activation of RAC1 and ARF6. Once these exciting results are rigorously confirmed and more information is obtained through our studies, we will focus on our second goal of determining whether CD24, RCC2, or the ratio of CD24/RCC2 can serve as biomarkers for early detection of tumor metastasis in prostate cancer. Unfortunately, anti-tumor drugs have failed to cure patients with late-stage tumor metastasis. Currently, early detection is an effective way to improve treatment for patients with tumor metastasis. Our proposed work will not only help us understand how prostate cancer metastasizes, but will also tell us which biomarkers may be useful for predicting tumor metastasis. If our hypothesis is validated, our findings will identify gene targets that may lead to the development of more effective treatment options for patients with early metastatic prostate cancer. If CD24, RCC2, or other molecules regulated by these genes are validated as early metastatic biomarkers, our proposed work will help clinical doctors to diagnose patients with tumor metastasis early, at prostatic biopsy. Thus, the proposed project will address the Prostate Cancer Research Program s overarching challenges: "Develop better tools for early detection of clinically relevant disease" and "Distinguish aggressive from indolent disease in men newly diagnosed with prostate cancer."
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510323
Entities
People
- Runhua Liu
Organizations
- United States Army
- University of Alabama at Birmingham