Histochemistry and Cell Biology

, 133:113

Melanoma progression exhibits a significant impact on connexin expression patterns in the epidermal tumor microenvironment

  • Nikolas K. Haass
  • D. Ripperger
  • E. Wladykowski
  • P. Dawson
  • P. A. Gimotty
  • C. Blome
  • F. Fischer
  • P. Schmage
  • I. Moll
  • Johanna M. Brandner
Original Paper

DOI: 10.1007/s00418-009-0654-5

Cite this article as:
Haass, N.K., Ripperger, D., Wladykowski, E. et al. Histochem Cell Biol (2010) 133: 113. doi:10.1007/s00418-009-0654-5

Abstract

Melanoma depends on, interacts with and reacts to the stroma in which it is embedded, including fibroblasts, extracellular matrix, endothelial cells and immune cells. However, the impact of melanoma on the epidermal tumor microenvironment—the multilayered epithelium of the skin—is poorly understood. Gap junctions are essential for intercellular communication and involved in proliferation, differentiation and homeostasis of keratinocytes. We have shown previously that the gap junction proteins connexin 26 and 30 (Cx26 and Cx30) are induced in the epidermal tumor microenvironment of skin cancers including melanoma. This study compares the extent of Cx26, Cx30 and Cx43 expression in the epidermal microenvironment of melanocytic nevi and melanomas and its association with melanoma thickness, proliferative index of the tumor and its microenvironment, and with 5-year metastasis and survival. We found that induction of Cx26 and Cx30 cell–cell border expression in the epidermal tumor microenvironment correlates to malignancy. Importantly, there was a significant correlation of tumor thickness with the vertical epidermal Cx26 and Cx30 expression pattern and the horizontal Cx26 dissemination. Furthermore, horizontal Cx26 expression correlated with metastasis. Vertical epidermal expression patterns of Cx26 and Cx30 significantly correlated with the proliferative index in the epidermal tumor microenvironment but not with the proliferative index in the tumor. In contrast, Cx43 did not correlate with malignancy, thickness or proliferative index. In summary, here we show for the first time a significant association between the progression of melanoma and alterations in its epithelial tumor microenvironment.

Keywords

Cell–cell communication Gap junctions Cx26 Cx30 Skin cancer Carcinogenesis 

Abbreviations

Cx

Connexin(s)

GJ

Gap junction

GJIC

Gap junctional intercellular communication

Supplementary material

418_2009_654_MOESM1_ESM.doc (54 kb)
Supplementary material 1 (DOC 53 kb)

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Nikolas K. Haass
    • 1
    • 2
    • 3
    • 4
  • D. Ripperger
    • 1
  • E. Wladykowski
    • 1
  • P. Dawson
    • 5
  • P. A. Gimotty
    • 5
  • C. Blome
    • 6
  • F. Fischer
    • 7
  • P. Schmage
    • 7
  • I. Moll
    • 1
  • Johanna M. Brandner
    • 1
  1. 1.Department of Dermatology and VenerologyUniversity Hospital Hamburg-EppendorfHamburgGermany
  2. 2.Discipline of Dermatology, Faculty of Medicine, Central Clinical SchoolUniversity of SydneySydneyAustralia
  3. 3.Centenary Institute of Cancer Medicine and Cell BiologyNewtownAustralia
  4. 4.The Wistar InstitutePhiladelphiaUSA
  5. 5.Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and BiostatisticsAbramson Cancer Center, University of PennsylvaniaPhiladelphiaUSA
  6. 6.German Center for Health Services Research in Dermatology (CVderm)University Hospital Hamburg-EppendorfHamburgGermany
  7. 7.Department of Restorative and Preventive DentistryUniversity Hospital Hamburg-EppendorfHamburgGermany