2/2 Pilot Project 2: Langston University-UNTHSC Partnership for Cancer Research and Education

研究摘要： 前列腺癌细胞定植于骨环境并对其产生抵抗力的机制 防治前列腺癌骨转移是提高晚期前列腺癌生存率的关键 癌症患者。膜联蛋白A2(AnxA2)在转移性前列腺癌中的高表达及促进细胞生长 通过激活纤溶酶原和裂解细胞外基质进行迁移和侵袭。AnxA2扮演着至关重要的角色 在造血干细胞定位到骨髓的壁龛中。AnxA2作为一种黏附分子 调节成骨分化，但其分子机制尚不清楚。我们假设PTEN 丢失或突变导致AnxA2移位增加到细胞外表面，从而促进前列腺 肿瘤转移至骨。这一假设的理论基础是基于我们的发现，该发现证明了更高的 PTEN缺失和突变的前列腺癌细胞株与野生型细胞表面AnxA2表达的比较 PTEN前列腺癌细胞系PTEN缺失或缺失时Tyr-23位AnxA2磷酸化增强 突变的前列腺癌细胞系。拟议研究的目标是建立PTEN和PTEN之间的相关性 前列腺癌AnxA2基因缺失及细胞表面表达增强此外，我们还将确定 AnxA2是前列腺癌骨转移的重要现象。拟议的工作将加强我们的 了解细胞表面AnxA2在前列腺癌骨转移中的作用 用作重要的治疗靶点。拟议的工作将为 开发一种新的靶向疗法，可能转化为针对晚期癌症的有效治疗方案 前列腺癌。

Research Summary: The mechanism by which the prostate cancer cells colonize the bone environment and develop resistance to prevent or treat prostate cancer bone metastasis is critical to increase the survival rate of advanced prostate cancer patients. Annexin A2 (AnxA2) protein is overexpressed in metastatic prostate tumors and promotes cell migration and invasion by activating plasminogen and cleaving extracellular matrix. AnxA2 plays a critical role in hematopoietic stem cell localization to the marrow niche. AnxA2 serves as an adhesion molecule and regulates osteogenic differentiation, yet the molecular mechanisms remain unclear. We hypothesize that PTEN loss or mutation causes the increased translocation of AnxA2 to the outer cell surface which promotes prostate tumor metastasis to bone. The rationale for this hypothesis is based on our findings that demonstrated the higher expression of cell surface AnxA2 in PTEN null or mutated prostate cancer cell lines compared to wild-type PTEN prostate cancer cell lines because of increased phosphorylation of AnxA2 at Tyr-23 in PTEN null or mutated prostate cancer cell lines. The goal of the proposed study is to establish the correlation between PTEN loss and increased cell surface expression of AnxA2 in prostate cancer. In addition, we will establish that AnxA2 is an important phenomenon for prostate tumor bone metastasis. The proposed work will enhance our understanding on the role of cell surface AnxA2 in prostate cancer bone metastasis and could potentially be used as an important therapeutic target. The proposed work will provide the stepping stones for the development of a novel targeted therapy that may translate into an effective treatment regimen against advanced prostate cancer.