Loss of primary cilia occurs early in breast cancer development

Persistent Link:
http://hdl.handle.net/10150/610119
Title:
Loss of primary cilia occurs early in breast cancer development
Author:
Menzl, Ina; Lebeau, Lauren; Pandey, Ritu; Hassounah, Nadia; Li, Frank; Nagle, Ray; Weihs, Karen; McDermott, Kimberly
Affiliation:
The University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA; Department of Pathology, University of Arizona Medical Center, Tucson, AZ, USA; Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA; Department of Psychiatry, University of Arizona Medical Center, Tucson, AZ, USA; Bio5 Institute, University of Arizona, Tucson, AZ, USA
Issue Date:
2014
Publisher:
BioMed Central
Citation:
Menzl et al. Cilia 2014 2014, 3:7 http://www.ciliajournal.com/content/3/1/7
Journal:
Cilia
Rights:
© Menzl et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
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.
EISSN:
2046-2530
DOI:
10.1186/2046-2530-3-7
Keywords:
Primary cilia; Invasive breast cancer; Carcinoma in situ; Cancer-associated stroma; Ciliogenesis; Cilia length
Version:
Final published version
Additional Links:
http://www.ciliajournal.com/content/3/1/7

Full metadata record

DC FieldValue Language
dc.contributor.authorMenzl, Inaen
dc.contributor.authorLebeau, Laurenen
dc.contributor.authorPandey, Rituen
dc.contributor.authorHassounah, Nadiaen
dc.contributor.authorLi, Franken
dc.contributor.authorNagle, Rayen
dc.contributor.authorWeihs, Karenen
dc.contributor.authorMcDermott, Kimberlyen
dc.date.accessioned2016-05-20T08:59:02Z-
dc.date.available2016-05-20T08:59:02Z-
dc.date.issued2014en
dc.identifier.citationMenzl et al. Cilia 2014 2014, 3:7 http://www.ciliajournal.com/content/3/1/7en
dc.identifier.doi10.1186/2046-2530-3-7en
dc.identifier.urihttp://hdl.handle.net/10150/610119-
dc.description.abstractBACKGROUND: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.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://www.ciliajournal.com/content/3/1/7en
dc.rights© Menzl et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)en
dc.subjectPrimary ciliaen
dc.subjectInvasive breast canceren
dc.subjectCarcinoma in situen
dc.subjectCancer-associated stromaen
dc.subjectCiliogenesisen
dc.subjectCilia lengthen
dc.titleLoss of primary cilia occurs early in breast cancer developmenten
dc.typeArticleen
dc.identifier.eissn2046-2530en
dc.contributor.departmentThe University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USAen
dc.contributor.departmentDepartment of Pathology, University of Arizona Medical Center, Tucson, AZ, USAen
dc.contributor.departmentDepartment of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USAen
dc.contributor.departmentDepartment of Psychiatry, University of Arizona Medical Center, Tucson, AZ, USAen
dc.contributor.departmentBio5 Institute, University of Arizona, Tucson, AZ, USAen
dc.identifier.journalCiliaen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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