The influence of different microenvironments on melanoma invasiveness and microcirculation patterns: an animal experiment study in the mouse model

J Cancer Res Clin Oncol. 2007 Dec;133(12):979-85. doi: 10.1007/s00432-007-0245-6. Epub 2007 Jun 16.

Abstract

Object: To investigate the influence of different microenvironments on tumor microcirculation patterns and invasiveness capability.

Methods: Melanoma B16 cells were injected into the abdominal cavity and skeletal muscle of C57 mice synchronously. CK-18 expression in melanoma was assessed to distinguish the malignant phenotype of tumors in the abdominal cavity from that in the skeletal muscle. HIF-1alpha, MMP-2 and MMP-9 expression and mRNA levels of MMP-2 and MMP-9 was detected to compare the mRNA levels of MMP-2 and MMP-9 from the two microenvironments. Cells positive for each immunohistochemical stain and the vessels representative of each type of microcirculation pattern were counted in two microenvironments.

Results: CK-18 and HIF-1alpha expression of melanoma were significantly higher in the skeletal muscle than in the abdominal cavity (P<0.05). Compared with the abdominal cavity, melanoma cells in the skeletal muscle overexpressed MMP-2 and MMP-9 (P<0.05). Real time-PCR results also showed that MMP-2 and MMP-9 mRNA levels of melanoma were higher in the skeletal muscle than in the abdominal cavity (P<0.05). VM channels and endothelium-dependent vessels were the major microcirculation pattern in the skeletal muscle and in the abdominal cavity, respectively.

Conclusion: Different microenvironments affect invasiveness and blood supply patterns of melanoma.

MeSH terms

  • Abdominal Cavity
  • Animals
  • Endothelium, Vascular
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Keratin-18 / metabolism
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9 / metabolism
  • Melanoma, Experimental / blood supply*
  • Melanoma, Experimental / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Microcirculation*
  • Muscle, Skeletal
  • Neoplasm Invasiveness*
  • Neoplasm Transplantation
  • Neovascularization, Pathologic*

Substances

  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Keratin-18
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9