Abstract

Prostate cancer is the most commonly diagnosed malignancy for men in the United States. Metastatic prostate cancer, the lethal form of the disease, has a life expectancy of approximately five years. Identification of factors associated with this transition to metastatic disease is crucial for future therapies. One such factor is the SSX gene family, a family of cancer/testis antigens (CTA) transcription factors which have been shown to be aberrantly expressed in other cancers and associated with the epithelial to mesenchymal transition (EMT). We have previously shown that SSX expression in prostate cancers was restricted to metastatic tissue and not primary tumors. In this study, we have identified SSX2 as the predominant SSX family member expressed in prostate cancer, and found its expression in the peripheral blood of 19 of 54 (35%) prostate cancer patients, with expression restricted to circulating tumor cells, and in 7 of 15 (47%) metastatic cDNA samples. Further, we examined SSX2 function in prostate cancer through knockdown and overexpression in prostate cancer cell lines. While overexpression had little effect on morphology or gene transcript changes, knockdown of SSX2 resulted in an epithelial morphology, increased cell proliferation, increased expression of genes involved in focal adhesion, decreased anchorage independent growth, increased invasion, and increased tumorigenicity in vivo. We conclude from these findings that SSX2 expression in prostate cancer is not a driver of EMT, but is involved in processes associated with EMT including loss of focal adhesion that may be related to tumor cell dissemination.

Highlights

  • Prostate cancer is the most commonly diagnosed malignancy of men in the United States [1]

  • In this study we have shown SSX2 is the primary member of the SSX family expressed in prostate cancer, expressed in metastases and in circulating tumor cells

  • We found SSX2 is involved with genes associated with epithelial to mesenchymal transition (EMT) and affects genes involved with cell adhesion

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Summary

Introduction

Prostate cancer is the most commonly diagnosed malignancy of men in the United States [1]. Metastatic prostate cancer, and metastatic disease progressing beyond initial androgen deprivation therapy is lethal, with a life expectancy of approximately five years [4]. The SSX family of proteins are cancer-testis antigens (CTAs), a group of proteins whose normal expression is restricted to immune-privileged testis germline cells, but display aberrant heightened expression in many different types of cancer [9, 10]. These immuneprivileged germ cell tissues lack HLA class I molecules [11]. We previously screened the sera of prostate cancer patients against an expression library of 29 CTA family members, and identified SSX2 as one of the most commonly recognized CT antigens [13]

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