Depletion of cutaneous macrophages and dendritic cells promotes growth of basal cell carcinoma in mice

PLoS One. 2014 Apr 1;9(4):e93555. doi: 10.1371/journal.pone.0093555. eCollection 2014.

Abstract

Basal cell carcinoma (BCC) belongs to the group of non-melanoma skin tumors and is the most common tumor in the western world. BCC arises due to mutations in the tumor suppressor gene Patched1 (Ptch). Analysis of the conditional Ptch knockout mouse model for BCC reveals that macrophages and dendritic cells (DC) of the skin play an important role in BCC growth restraining processes. This is based on the observation that a clodronate-liposome mediated depletion of these cells in the tumor-bearing skin results in significant BCC enlargement. The depletion of these cells does not modulate Ki67 or K10 expression, but is accompanied by a decrease in collagen-producing cells in the tumor stroma. Together, the data suggest that cutaneous macrophages and DC in the tumor microenvironment exert an antitumor effect on BCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis / genetics*
  • Carcinoma, Basal Cell / drug therapy
  • Carcinoma, Basal Cell / genetics*
  • Carcinoma, Basal Cell / metabolism
  • Carcinoma, Basal Cell / pathology
  • Clodronic Acid / administration & dosage
  • Dendritic Cells / drug effects
  • Dendritic Cells / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liposomes / administration & dosage
  • Macrophages / drug effects
  • Macrophages / pathology
  • Mice
  • Mice, Knockout
  • Mutation
  • Patched Receptors
  • Patched-1 Receptor
  • Receptors, Cell Surface / genetics*
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / genetics

Substances

  • Liposomes
  • PTCH1 protein, human
  • Patched Receptors
  • Patched-1 Receptor
  • Ptch1 protein, mouse
  • Receptors, Cell Surface
  • Clodronic Acid

Grants and funding

This work was supported by the Deutsche Forschungsgemeinschaft (http://www.dfg.de/; FOR942 HA 2197/5-2 to Heidi Hahn). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.