Abstract A64: ASPORIN expression is associated with prostate cancer progression and bone metastasis

Abstract

Abstract Being one of the most common male cancers in western countries, prostate cancer (CaP) is also considered as a leading cause of cancer-related death. Advanced CaP patients display characteristically bone metastasis, a devastating and incurable phase which leads to patient morbidity and mortality. It is widely recognized that bone metastases are intimately associated with bone remodeling, resulting from interactions between tumor cells, tumor-associated stromal cells and bone cells. The understanding of molecular events involving in tumor-stroma, tumor-bone cells cross-talks may help to identify new mechanism in prostate cancer progression, new diagnostic markers as well as therapeutic targets. Here, we report for the first time the expression profile of ASPORIN (ASPN) in human primary prostate cancer and associated bone metastasis. ASPN is a member of the class I small leucine-rich proteoglycan (SLRP) family. This matrix protein has been showed to be involved in the inhibition of Transforming Growth Factor Beta (TGFβ) signaling pathway in cartilage, and its capacity to bind type-I collagen and calcium suggests its role in bone-forming osteoblast collagen mineralization processes. By RT-PCR, our results showed that ASPN gene transcript was up-regulated in human primary CaP tissues. Immunohistochemical staining of ASPN protein reveals its expression in CaP tumor-associated stromal cells. Using an experimental mouse bone metastasis model, we showed strong ASPN expression not only in tumor-associated stromal cells, but also in CaP tumor adjacent mouse osteoclasts and osteoblasts. Similar ASPN expression profile was identified in human CaP bone metastasis samples. Further studies of immunohistochemical staining on CaP tissue microarray suggested ASPN stromal expression profile was significantly associated with disease progression, which was confirmed by the results of metaanalysis of 167 nonmalignant, primary and metastatic prostate cancer DNA microarrays. Taken together, all these findings strongly suggest that ASPN could be potentially used to predict the aggressiveness of prostate cancer and bone metastasis. Meanwhile, this secreted protein localized in tumor cell microenvironment may influence prostate cancer cell behavior. Since ASPN has been shown to be involved in TGFβ signaling regulation in cartilage, it could also be involved in the osteoblastic/mixture lesion progression in bone in which this pathway plays an important role. Citation Format: Tian V. Tian, Sebastien Flajollet, Martine Duterque-Coquillaud, Diane Goltz, Sven Perner, Anne Flourens, Nathalie Tomavo, Edith Bonnelye, Yvan de Launoit, Nicolas Wernert, Xavier Leroy. ASPORIN expression is associated with prostate cancer progression and bone metastasis [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A64.