Potential therapeutic effect of the secretome from human uterine cervical stem cells against both cancer and stromal cells compared with adipose tissue stem cells

Oncotarget. 2014 Nov 15;5(21):10692-708. doi: 10.18632/oncotarget.2530.

Abstract

Evidences indicate that tumor development and progression towards a malignant phenotype depend not only on cancer cells themselves, but are also deeply influenced by tumor stroma reactivity. The present study uses mesenchymal stem cells from normal human uterine cervix (hUCESCs), isolated by the minimally invasive method of routine Pap cervical smear, to study their effect on the three main cell types in a tumor: cancer cells, fibroblasts and macrophages. Administration of hUCESCs-conditioned medium (CM) to a highly invasive breast cancer MDA-MB-231 cell line and to human breast tumors with high cell proliferation rates had the effect of reducing cell proliferation, modifying the cell cycle, inducing apoptosis, and decreasing invasion. In a xenograft mouse tumor model, hUCESCs-CM reduced tumor growth and increased overall survival. In cancer-associated fibroblasts, administration of hUCESCs-CM resulted in reduced cell proliferation, greater apoptosis and decreased invasion. In addition, hUCESCs-CM inhibited and reverted macrophage differentiation. The analysis of hUCESCs-CM (fresh and lyophilized) suggests that a complex paracrine signaling network could be implicated in the anti-tumor potential of hUCESCs. In light of their anti-tumor potential, the easy cell isolation method, and the fact that lyophilization of their CM conserves original properties make hUCESCs good candidates for experimental or clinical applications in anticancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Adipose Tissue / metabolism*
  • Animals
  • Apoptosis
  • Blotting, Western
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Cycle
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Cervix Uteri / cytology
  • Cervix Uteri / metabolism*
  • Culture Media, Conditioned / pharmacology
  • Female
  • Flow Cytometry
  • Humans
  • Immunoenzyme Techniques
  • Macrophages / cytology
  • Macrophages / metabolism
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, SCID
  • Proteome / metabolism
  • Proteome / pharmacology*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism
  • Stromal Cells / pathology*
  • Xenograft Model Antitumor Assays

Substances

  • Culture Media, Conditioned
  • Proteome