Keratin 13 Is Enriched in Prostate Tubule-Initiating Cells and May Identify Primary Prostate Tumors that Metastasize to the Bone
Publication Date
October 06, 2016
Journal
PLOS ONE
Authors
Sandy Liu, Radu M. Cadaneanu, Baohui Zhang, Lihong Huo, et al
Volume
11
Issue
10
Pages
e0163232
DOI
https://dx.plos.org/10.1371/journal.pone.0163232
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0163232
Scopus
84990946939
Mendeley
http://www.mendeley.com/research/keratin-13-enriched-prostate-tubuleinitiating-cells-identify-primary-prostate-tumors-metastasize-bon
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Mendeley | Further Information

{"title"=>"Keratin 13 is enriched in prostate tubule-initiating cells and may identify primary prostate tumors that metastasize to the bone", "type"=>"journal", "authors"=>[{"first_name"=>"Sandy", "last_name"=>"Liu", "scopus_author_id"=>"57191494197"}, {"first_name"=>"Radu M.", "last_name"=>"Cadaneanu", "scopus_author_id"=>"55183904500"}, {"first_name"=>"Baohui", "last_name"=>"Zhang", "scopus_author_id"=>"55720932200"}, {"first_name"=>"Lihong", "last_name"=>"Huo", "scopus_author_id"=>"35083658400"}, {"first_name"=>"Kevin", "last_name"=>"Lai", "scopus_author_id"=>"56583353300"}, {"first_name"=>"Xinmin", "last_name"=>"Li", "scopus_author_id"=>"56803027500"}, {"first_name"=>"Colette", "last_name"=>"Galet", "scopus_author_id"=>"56605131400"}, {"first_name"=>"Tristan R.", "last_name"=>"Grogan", "scopus_author_id"=>"55531342100"}, {"first_name"=>"David", "last_name"=>"Elashoff", "scopus_author_id"=>"6603363813"}, {"first_name"=>"Stephen J.", "last_name"=>"Freedland", "scopus_author_id"=>"7003419852"}, {"first_name"=>"Matthew", "last_name"=>"Rettig", "scopus_author_id"=>"7003447821"}, {"first_name"=>"William J.", "last_name"=>"Aronson", "scopus_author_id"=>"7003902791"}, {"first_name"=>"Beatrice S.", "last_name"=>"Knudsen", "scopus_author_id"=>"7004937729"}, {"first_name"=>"Michael S.", "last_name"=>"Lewis", "scopus_author_id"=>"56407225700"}, {"first_name"=>"Isla P.", "last_name"=>"Garraway", "scopus_author_id"=>"6507510982"}], "year"=>2016, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"612637621", "pmid"=>"27711225", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0163232", "isbn"=>"1932-6203", "scopus"=>"2-s2.0-84990946939", "sgr"=>"84990946939"}, "id"=>"be39b402-c488-3e8c-bcb2-b96c385055c7", "abstract"=>"Background: Benign human prostate tubule-initiating cells (TIC) and aggressive prostate cancer display common traits, including tolerance of low androgen levels, resistance to apoptosis, and microenvironment interactions that drive epithelial budding and outgrowth. TIC can be distinguished from epithelial and stromal cells that comprise prostate tissue via cell sorting based upon Epcam, CD44, and CD49f antigenic profiles. Fetal prostate epithelial cells (FC) possess a similar antigenic profile to adult TIC and are capable of inducing tubule formation. To identify the TIC niche in human prostate tissue, differential keratin (KRT) expression was evaluated. Results: Gene expression data generated from Affymetrix Gene Chip human U133 Plus 2.0 array of sorted adult and fetal epithelial cells revealed KRT13 to be significantly enriched in FC and TIC compared to basal cells (BC) and luminal cells (LC) (p<0.001). Enriched KRT13 expression was confirmed by RT-PCR and cytospin immunostaining. Immunohistochemical analysis of KRT13 expression revealed rare KRT13+ epithelia throughout prostatic ducts/acini in adult tissue specimens and differentiated tubules in 24-week recombinant grafts, In contrast, abundant KRT13 expression was observed in developing ducts/acini in fetal prostate and cord-like structures composing 8-week recombinant grafts. Immunostaining of a prostate tissue microarray revealed KRT13+ tumor foci in approximately 9% of cases, and this subset displayed significantly shorter time to recurrence (p = 0.031), metastases (p = 0.032), and decreased overall survival (p = 0.004). Diagnostic prostate needle biopsies (PNBX) from untreated patients with concurrent bone metastases (clinical stage M1) displayed KRT13+ tumor foci, as did bone metastatic foci. Conclusions: The expression profile of KRT13 in benign fetal and adult prostate tissue and in recombinant grafts, as well as the frequency of KRT13 expression in primary and metastatic prostate cancer indicates that it may be a marker of a stem/progenitor-like cell state that is co-opted in aggressive tumor cells. KRT13 is enriched in benign stem-like cells that display androgen-resistance, apoptosis-resistance, and branching morphogenesis properties. Collectively our data demonstrate that KRT13 expression is associated with poor prognosis at multiple stages of disease progression and may represent an important biomarker of adverse outcome in patients with prostate cancer.", "link"=>"http://www.mendeley.com/research/keratin-13-enriched-prostate-tubuleinitiating-cells-identify-primary-prostate-tumors-metastasize-bon", "reader_count"=>11, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Librarian"=>2, "Researcher"=>1, "Student > Postgraduate"=>1, "Other"=>2, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Librarian"=>2, "Researcher"=>1, "Student > Postgraduate"=>1, "Other"=>2, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>4, "Agricultural and Biological Sciences"=>3, "Chemical Engineering"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>2}, "Chemical Engineering"=>{"Chemical Engineering"=>1}}, "group_count"=>0}

Scopus | Further Information

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