Adipose-Derived Stem Cells of Blind Mole Rat Spalax Exhibit Reduced Homing Ability: Molecular Mechanisms and Potential Role in Cancer Suppression

Anatolii Mamchur, Eva Leman, Safaa Salah, Aaron Avivi, Imad Shams, Irena Manov

Research output: Contribution to journalArticlepeer-review

Abstract

Adipose-derived stem cells (ADSCs) are recruited by cancer cells from the adjacent tissue, and they become an integral part of the tumor microenvironment. Here, we report that ADSCs from the long-living, tumor-resistant blind mole rat, Spalax, have a low ability to migrate toward cancer cells compared with cells from its Rattus counterpart. Tracking 5-ethynyl-2′-deoxyuridine (EdU)-labeled ADSCs, introduced to tumor-bearing nude mice, toward the xenografts, we found that rat ADSCs intensively migrated and penetrated the tumors, whereas only a few Spalax ADSCs reached the tumors. Moreover, rat ADSCs, but not Spalax ADSCs, acquired endothelial-like phenotype and incorporated in the intratumoral reticular structure resembling a vasculature. Likewise, endothelial-like cells differentiated from Spalax and rat ADSCs could form capillary-like structures; however, the tube densities were higher in rat-derived cells. Using time-lapse microscopy, in vitro wound-healing, and transwell migration assays, we demonstrated the impaired motility and low polarization ability of Spalax ADSCs. To assess whether the phosphorylated status of myosin light chain (MLC) is involved in the decreased motility of Spalax ADSCs, we inhibited MLC phosphorylation by blocking of Rho-kinase (ROCK). Inhibition of ROCK resulted in the suppression of MLC phosphorylation, acquisition of actin polarization, and activation of motility and migration of Spalax ADSCs. We propose that reduced ADSCs migration to cancer and poor intratumoral angiogenesis play a role in Spalax’s cancer resistance. Learning more about the molecular strategy of noncancerous cells in Spalax to resist oncogenic stimuli and maintain a nonpermissive tumor milieu may lead us to developing new cancer-preventive strategy in humans. Stem Cells 2018;36:1630–1642.

Original languageEnglish
Pages (from-to)1630-1642
Number of pages13
JournalStem Cells
Volume36
Issue number10
DOIs
StatePublished - Oct 2018

Bibliographical note

Funding Information:
This study was supported by a grant from the John Templeton Foundation (# 53057) and by a generous donation from the Kadas Family Charitable Foundation. I.M. was supported by the Ministry of Immigrant Absorption and the Committee for Planning and Budgeting of the Council for Higher Education, Israel, within the framework of the KAMEA program. We thank Dr. Rami Reshef for help and guidance with histological techniques, Mrs. Yulia Pollak for help in microscopy and Dr. Sagie Schif-Zuck for assistance in flow cytometry studies.

Publisher Copyright:
© AlphaMed Press 2018

Keywords

  • Adipose-derived stem cells
  • Mesenchymal stem cell motility
  • Myosin light chain
  • Spalax
  • Tumor microenvironment

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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