Primary Cilia Are Lost in Preinvasive and Invasive Prostate Cancer

Nadia B. Hassounah, Raymond B Nagle, Kathylynn Saboda, Denise Roe, Bruce L. Dalkin, Kimberly McDermott

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Prostate cancer is the second most commonly diagnosed cancer in men worldwide. Little is known about the role of primary cilia in preinvasive and invasive prostate cancer. However, reduced cilia expression has been observed in human cancers including pancreatic cancer, renal cell carcinoma, breast cancer, cholangiocarcinoma, and melanoma. The aim of this study was to characterize primary cilia expression in preinvasive and invasive human prostate cancer, and to investigate the correlation between primary cilia and the Wnt signaling pathway. Human prostate tissues representative of stages of prostate cancer formation (normal prostate, prostatic intraepithelial neoplasia (PIN), and invasive prostate cancer (including perineural invasion)) were stained for ciliary proteins. The frequency of primary cilia was determined. A decrease in the percentage of ciliated cells in PIN, invasive cancer and perineural invasion lesions was observed when compared to normal. Cilia lengths were also measured to indirectly test functionality. Cilia were shorter in PIN, cancer, and perineural invasion lesions, suggesting dysfunction. Primary cilia have been shown to suppress the Wnt pathway. Increased Wnt signaling has been implicated in prostate cancer. Therefore, we investigated a correlation between loss of primary cilia and increased Wnt signaling in normal prostate and in preinvasive and invasive prostate cancer. To investigate Wnt signaling in our cohort, serial tissue sections were stained for β-catenin as a measure of Wnt signaling. Nuclear β-catenin was analyzed and Wnt signaling was found to be higher in un-ciliated cells in the normal prostate, PIN, a subset of invasive cancers, and perineural invasion. Our results suggest that cilia normally function to suppress the Wnt signaling pathway in epithelial cells and that cilia loss may play a role in increased Wnt signaling in some prostate cancers. These results suggest that cilia are dysfunctional in human prostate cancer, and increase Wnt signaling occurs in a subset of cancers.

Original languageEnglish (US)
Article numbere68521
JournalPLoS One
Volume8
Issue number7
DOIs
StatePublished - Jul 2 2013

Fingerprint

Cilia
prostatic neoplasms
cilia
Prostatic Neoplasms
neoplasms
Prostatic Intraepithelial Neoplasia
Wnt Signaling Pathway
Prostate
Catenins
Neoplasms
lesions (animal)
Tissue
kidney neoplasms
pancreatic neoplasms
Cholangiocarcinoma
kidney cells
melanoma
Pancreatic Neoplasms
Renal Cell Carcinoma
Cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Primary Cilia Are Lost in Preinvasive and Invasive Prostate Cancer. / Hassounah, Nadia B.; Nagle, Raymond B; Saboda, Kathylynn; Roe, Denise; Dalkin, Bruce L.; McDermott, Kimberly.

In: PLoS One, Vol. 8, No. 7, e68521, 02.07.2013.

Research output: Contribution to journalArticle

Hassounah, Nadia B. ; Nagle, Raymond B ; Saboda, Kathylynn ; Roe, Denise ; Dalkin, Bruce L. ; McDermott, Kimberly. / Primary Cilia Are Lost in Preinvasive and Invasive Prostate Cancer. In: PLoS One. 2013 ; Vol. 8, No. 7.
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