Tumorspheres derived from prostate cancer cells possess chemoresistant and cancer stem cell properties

J Cancer Res Clin Oncol. 2012 Apr;138(4):675-86. doi: 10.1007/s00432-011-1146-2. Epub 2012 Jan 12.

Abstract

Purpose: Prostate cancer (PCa) becomes lethal when cancer cells develop into castration-resistant PCa, which remains incurable because of the poor understanding of their cell origin and characteristics. We aim to investigate the potential role of cancer stem cells (CSCs) in PCa progression.

Methods: Human PCa cell lines (LNCaP, 22RV1, DU145 and PC-3) were plated in serum-free suspension culture system allowed for tumorsphere forming. To evaluate the CSC characteristics of tumorspheres, the self-renewal, chemoresistance, tumorigenicity of the PCa tumorsphere cells, and the expression levels of stemness-related proteins in the PCa tumorsphere cells were assessed, comparing with the parental adherent cells.

Results: Tumorsphere cells from PCa cell lines displayed enhanced self-renewal, chemoresistance and tumor-initiating capacity when compared with the adherent cells. Additionally, these cells overexpressed CSC marker CD44. Also, the tumorsphere cells expressed high levels of "stemness" genes Gli1, ABCG2 and Bmi-1.

Conclusions: Collectively, these data demonstrated that tumorspheres derived from PCa cells possess chemoresistant and CSC properties. Our study suggests that the identification of PCa CSCs could provide new insight into the lethal phenotype of PCa and therapeutic implications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Antineoplastic Agents / pharmacology
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Docetaxel
  • Doxorubicin / pharmacology
  • Drug Resistance, Neoplasm*
  • Humans
  • Hyaluronan Receptors / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Proteins / metabolism
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Nuclear Proteins / metabolism
  • Polycomb Repressive Complex 1
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Proto-Oncogene Proteins / metabolism
  • Repressor Proteins / metabolism
  • Spheroids, Cellular / drug effects
  • Spheroids, Cellular / metabolism*
  • Spheroids, Cellular / pathology
  • Taxoids / pharmacology
  • Transcription Factors / metabolism
  • Transplantation, Heterologous
  • Tumor Burden
  • Vinblastine / pharmacology
  • Zinc Finger Protein GLI1

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents
  • BMI1 protein, human
  • GLI1 protein, human
  • Hyaluronan Receptors
  • Neoplasm Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Taxoids
  • Transcription Factors
  • Zinc Finger Protein GLI1
  • Docetaxel
  • Vinblastine
  • Doxorubicin
  • Polycomb Repressive Complex 1