Keratin 13 Is Enriched in Prostate Tubule-Initiating Cells and May Identify Primary Prostate Tumors that Metastasize to the Bone
| Autor: | Xin-Min Li, Colette Galet, Tristan Grogan, Baohui Zhang, Matthew Rettig, Beatrice S. Knudsen, Stephen J. Freedland, Kevin Lai, Isla P. Garraway, Sandy T. Liu, William J. Aronson, Lihong Huo, Radu M. Cadaneanu, Michael S. Lewis, David Elashoff |
|---|---|
| Přispěvatelé: | Samant, Rajeev |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Keratinocytes Male Pathology Cellular differentiation Biopsy Gene Expression lcsh:Medicine Immunostaining Pathology and Laboratory Medicine Epithelium Prostate cancer Mice Prostate Animal Cells Stem Cell Research - Nonembryonic - Human Medicine and Health Sciences Needle Reproductive System Procedures lcsh:Science Cancer Staining Multidisciplinary Tissue microarray biology Prostate Cancer Biopsy Needle Prostate Diseases Cell Differentiation Basal Cells Radical Prostatectomy Gene Expression Regulation Neoplastic medicine.anatomical_structure Oncology Neoplastic Stem Cells Anatomy Cellular Types Research Article Biotechnology PCA3 Adult Urologic Diseases medicine.medical_specialty Stromal cell General Science & Technology Urology Surgical and Invasive Medical Procedures Bone Neoplasms Research and Analysis Methods 03 medical and health sciences Exocrine Glands Signs and Symptoms Diagnostic Medicine medicine Genetics Animals Humans Prostatectomy Neoplastic Surgical Excision CD44 lcsh:R Keratin-13 Biology and Life Sciences Cancers and Neoplasms Prostatic Neoplasms Epithelial Cells Cell Biology medicine.disease Stem Cell Research Survival Analysis Genitourinary Tract Tumors 030104 developmental biology Biological Tissue Gene Expression Regulation Specimen Preparation and Treatment biology.protein Lesions Prostate Gland lcsh:Q |
| Zdroj: | Liu, S; Cadaneanu, RM; Zhang, B; Huo, L; Lai, K; Li, X; et al.(2016). Keratin 13 Is Enriched in Prostate Tubule-Initiating Cells and May Identify Primary Prostate Tumors that Metastasize to the Bone. PLOS ONE, 11(10), e0163232. doi: 10.1371/journal.pone.0163232. UCLA: Retrieved from: http://www.escholarship.org/uc/item/5pk8p165 PloS one, vol 11, iss 10 PLoS ONE, Vol 11, Iss 10, p e0163232 (2016) PLoS ONE |
| DOI: | 10.1371/journal.pone.0163232. |
| Popis: | Author(s): Liu, Sandy; Cadaneanu, Radu M; Zhang, Baohui; Huo, Lihong; Lai, Kevin; Li, Xinmin; Galet, Colette; Grogan, Tristan R; Elashoff, David; Freedland, Stephen J; Rettig, Matthew; Aronson, William J; Knudsen, Beatrice S; Lewis, Michael S; Garraway, Isla P | Abstract: BackgroundBenign 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.ResultsGene 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) (pl0.001). 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.ConclusionsThe 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|