title: Loss of primary cilia occurs early in breast cancer development.
abstract: BACKGROUND
  Primary cilia are microtubule-based organelles that protrude from the cell surface. Primary cilia play a critical role in development and disease through regulation of signaling pathways including the Hedgehog pathway. Recent mouse models have also linked ciliary dysfunction to cancer. However, little is known about the role of primary cilia in breast cancer development. Primary cilia expression was characterized in cancer cells as well as their surrounding stromal cells from 86 breast cancer patients by counting cilia and measuring cilia length. In addition, we examined cilia expression in normal epithelial and stromal cells from reduction mammoplasties as well as histologically normal adjacent tissue for comparison.
  
  
  RESULTS
  We observed a statistically significant decrease in the percentage of ciliated cells on both premalignant lesions as well as in invasive cancers. This loss of cilia does not correlate with increased proliferative index (Ki67-positive cells). However, we did detect rare ciliated cancer cells present in patients with invasive breast cancer and found that these express a marker of basaloid cancers that is associated with poor prognosis (Cytokeratin 5). Interestingly, the percentage of ciliated stromal cells associated with both premalignant and invasive cancers decreased when compared to stromal cells associated with normal tissue. To understand how cilia may be lost during cancer development we analyzed the expression of genes required for ciliogenesis and/or ciliary function and compared their expression in normal versus breast cancer samples. We found that expression of ciliary genes were frequently downregulated in human breast cancers.
  
  
  CONCLUSIONS
  These data suggest that primary cilia are lost early in breast cancer development on both the cancer cells and their surrounding stromal cells.
authors.affiliation: The University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
authors.forename: Ina
authors.initials: I
authors.lastname: Menzl
authors.affiliation: Department of Pathology, University of Arizona Medical Center, Tucson, AZ, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Lebeau
authors.affiliation: The University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
authors.forename: Ritu
authors.initials: R
authors.lastname: Pandey
authors.affiliation: The University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
authors.forename: Nadia B
authors.initials: NB
authors.lastname: Hassounah
authors.affiliation: Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA.
authors.forename: Frank W
authors.initials: FW
authors.lastname: Li
authors.affiliation: The University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA ; Department of Pathology, University of Arizona Medical Center, Tucson, AZ, USA.
authors.forename: Ray
authors.initials: R
authors.lastname: Nagle
authors.affiliation: The University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA ; Department of Psychiatry, University of Arizona Medical Center, Tucson, AZ, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Weihs
authors.affiliation: The University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA ; Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA ; Bio5 Institute, University of Arizona, Tucson, AZ, USA.
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: McDermott
keywords: Cancer-associated stroma; Carcinoma in situ; Cilia length; Ciliogenesis; Invasive breast cancer; Primary cilia