Abstract 54: Differential plectin isoform expression correlates with aggressive prostate cancer phenotypes

Abstract

Abstract Introduction: Prostate cancer (PCa) is the most prevalent cancer amongst men and the second most common cause of cancer related-deaths in the US. Although PCa has a long latent period of development, clinically, the disease has very heterogeneous phenotypes ranging from indolent asymptomatic cases to very aggressive metastatic life threatening and lethal forms. The most critical clinical challenge in the management of the patients is identifying those individuals at risk of developing aggressive metastatic disease. Currently there are no biomarkers that accurately predict the aggressiveness of PCa based solely on standard clinicopathologic features. Our long term objective is to identify the molecules and characterize the mechanisms that are involved in PCa metastasis. We recently demonstrated that plectin is upregulated in aggressive versus non-aggressive forms of syngeneic prostate cancer cell lines. In this study, we show that PCa aggressive phenotype correlates with the over expression of specific plectin isoforms. Understanding the mechanism and roles of different plectin isoforms in the progression of PCa will potentially better discriminate the more aggressive metastatic forms and provide better treatment and clinical management opportunities of the disease. Methods: We have compared the mRNA and protein expression profiles of plectin isoforms in prostate cancer cell lines and prostatectomy tissues with different ethnic backgrounds and malignancy phenotypes. Validations of differentially expressed isoforms have been done by Western blot, qRT-PCR, siRNA knockdowns, proliferation assays and invasion assays, flow cytometry, IHC and IFA. Results: We demonstrate the correlation between the expression of specific isoforms with aggressive PCa. This was validated by Western blot, confocal microscopy and immunohistochemistry. SiRNA knockdown of specific plectin isoforms suppresses the invasive and migratory capacity of PCa cells. To our knowledge, this study is the first to demonstrate that differential expression of plectin isoforms correlates with the invasion and metastasis in PCa. Conclusions: We have identified plectin isoforms that are differentially expressed in PCa cells lines and prostatectomy tissues with different malignancy phenotypes. These findings are currently being validated using disease stratified TMAs. Further studies are focusing on uncovering the mechanisms responsible for progression and metastasis of PCa that are modulated by specific plectin isoforms. These could assist in the development of novel diagnostic and therapeutic strategies for the disease. Citation Format: Tanya C. Burch, Johng S. Rhim, Julius O. Nyalwidhe. Differential plectin isoform expression correlates with aggressive prostate cancer phenotypes. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 54. doi:10.1158/1538-7445.AM2014-54