Cancer Microenvironment

, Volume 5, Issue 1, pp 59–72

The Interrelating Dynamics of Hypoxic Tumor Microenvironments and Cancer Cell Phenotypes in Cancer Metastasis

Article

DOI: 10.1007/s12307-011-0067-6

Cite this article as:
Bartkowiak, K., Riethdorf, S. & Pantel, K. Cancer Microenvironment (2012) 5: 59. doi:10.1007/s12307-011-0067-6

Abstract

The interrelating dynamics of the primary tumor cells and their surrounding microenvironment might determine phenotypic characteristics of disseminated tumor cells and contribute to cancer metastasis. Cytoprotective mechanisms (e.g., energy metabolism control, DNA damage response, global translation control and unfolded protein response) exert selective pressure in the tumor microenvironment. In particular, adaptation to hypoxia is vital for survival of malignant cells in the tumor and at distant sites such as the bone marrow. In addition to the stress response, the ability of tumor cells to undergo certain cellular re-differentiation programmes like the epithelial-mesenchymal transition (EMT), which is linked to cancer stemness, appears to be important for successful cancer cell spread. Here we will discuss the selection pressures that eventually lead to the formation of overt metastases. We will focus the properties of the microenvironment including (i) metabolic and cytoprotective programs that ensure survival of disseminated tumor cells, (ii) blood vessel structure, and (iii) the hypoxia-normoxia switch as well as intrinsic factors affecting the evolvement of novel tumor cell populations.

Keywords

Bone marrow Disseminated tumor cells Epithelial-mesenchymal transition Hypoxia Stem cells Tumor microenvironment 

Abbreviations

ATF6

activating transcription factor 6

CTC

circulating tumor cells

CXCR4

C-X-C chemokine receptor 4

DTC

disseminated tumor cells

EGFR

epidermal growth factor receptor

EIF2

eukaryotic initiation factor 2

EMT

epithelial-mesenchymal transition

ER

endoplasmatic reticulum

HIF-1

hypoxia inducible factor 1

HR

homologous recombination

IRE1

inositol-requiring protein 1

MET

mesenchymal-epithelial transition

NHEJ

non-homologous end joining

PDI

protein disulfide isomerase

PERK

PKR-like ER kinase

PTEN

phosphatase and tensin homolog

ROS

reactive oxygen species

RTK

receptor tyrosine kinase

SDF1

stromal cell-derived factor 1

UPR

unfolded protein response

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Kai Bartkowiak
    • 1
  • Sabine Riethdorf
    • 1
  • Klaus Pantel
    • 1
  1. 1.Institute of Tumor BiologyUniversity Medical Center Hamburg-EppendorfHamburgGermany

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