Stem Cell Reviews and Reports

, Volume 6, Issue 2, pp 307–316

Epiblast/Germ Line Hypothesis of Cancer Development Revisited: Lesson from the Presence of Oct-4+ Cells in Adult Tissues

  • Mariusz Z. Ratajczak
  • Dong-Myung Shin
  • Rui Liu
  • Wojtek Marlicz
  • Maciej Tarnowski
  • Janina Ratajczak
  • Magda Kucia
Article

DOI: 10.1007/s12015-010-9143-4

Cite this article as:
Ratajczak, M.Z., Shin, DM., Liu, R. et al. Stem Cell Rev and Rep (2010) 6: 307. doi:10.1007/s12015-010-9143-4

Abstract

The morphology of several tumors mimics developmentally early tissues; tumors often express early developmental markers characteristic for the germ line lineage. Recently, our group identified a population of very small stem cells (SCs) in murine bone marrow (BM) and other adult organs that express several markers characteristic for epiblast/germ line-derived SCs. We named these rare cells “Very Small Embryonic/Epiblast-like Stem Cells (VSELs).” We hypothesized that these cells that express both epiblast and germ line markers are deposited during early gastrulation in developing tissues and organs and play an important role in the turnover of tissue-committed (TC) SCs. To support this, we envision that the germ line is not only the origin of SCs, but also remains as a scaffold or back-up for the SC compartment in adult life. Furthermore, we noticed that VSELs are protected from uncontrolled proliferation and teratoma formation by a unique DNA methylation pattern in some developmentally crucial imprinted genes, which show hypomethylation or erasure of imprints in paternally methylated genes and hypermethylation of imprints in the maternally methylated. In pathological situations, however, we hypothesize that VSELs could be involved in the development of several malignancies. Therefore, potential involvement of VSELs in cancerogenesis could support century-old concepts of embryonic rest- or germ line-origin hypotheses of cancer development. However, we are aware that this working hypothesis requires further direct experimental confirmation.

Keywords

VSELsOct-4Cancer testis antigensGerm line

Abbreviations

BM

Bone marrow

BMMNC

Bone marrow mononuclear cell

C/T

Cancer testis

DMR

Differently methylated region

dpc

Days post-conception

EGC

Embryonic germ cell

ESC

Embryonic stem cell

FACS

Fluorescence-activated cell sorting

FC

Flow cytometry

GC

Germ cell

HSC

Hematopoietic stem cell

ICM

Inner cell mass

Igf1R

Insulin-like growth factor 1 receptor

Igf2

Insulin-like growth factor 2

Igf2R

Igf2 receptor

ISS

ImageStream system

PGC

Primordial germ cell

PSC

Pluripotent stem cell

Rasgrf1

Ras protein-specific guanine nucleotide-releasing factor 1

SC

Stem cell

SSEA-1

Stage-specific embryonic antigen-1

TCSC

Tissue-committed stem cell

VSEL

Very small embryonic/epiblast-like stem cell

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Mariusz Z. Ratajczak
    • 1
  • Dong-Myung Shin
    • 1
  • Rui Liu
    • 1
  • Wojtek Marlicz
    • 2
  • Maciej Tarnowski
    • 1
  • Janina Ratajczak
    • 1
  • Magda Kucia
    • 1
  1. 1.Stem Cell Institute at the James Graham Brown Cancer CenterUniversity of LouisvilleLouisvilleUSA
  2. 2.Department of PathophysiologyPomeranian Medical UniversitySzczecinPoland