Vascular expression of matrix metalloproteinase-13 (collagenase-3) in basal cell carcinoma

Yukari Hattori1, Kamalakar C Nerusu, Narasimharao Bhagavathula

  • 1Department of Pathology, The University of Michigan, Ann Arbor 48109, USA.

Insights

Matrix metalloproteinase-13 (MMP-13) is found in blood vessels of basal cell carcinomas and normal skin. Endothelial cells express MMP-13, with expression increasing due to inflammatory signals and 3D collagen.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Dermatology

Background:

  • Matrix metalloproteinase-13 (MMP-13) is a collagenase implicated in tissue remodeling.
  • MMP-13's role in tumor vasculature and endothelial cells is not fully understood.

Purpose of the Study:

  • To investigate the presence and regulation of MMP-13 in the vasculature of human basal cell carcinomas (BCCs).
  • To determine if endothelial cells express MMP-13 and how its expression is modulated.

Main Methods:

  • Immunohistochemistry was used to detect MMP-13 in surgical specimens of BCC and normal skin.
  • Reverse transcription-polymerase chain reaction (RT-PCR), Southern blotting, and Western blotting were employed to assess MMP-13 expression in cultured endothelial cells.
  • Endothelial cells were treated with phorbol myristate acetate (PMA), interleukin-1alpha (IL-1alpha), and tumor necrosis factor-alpha (TNF-alpha) to study MMP-13 regulation.
  • Endothelial cells were cultured on different collagen matrices.

Main Results:

  • MMP-13 was detected in the vasculature of 17 of 20 human BCCs, while MMP-1 was found in only two.
  • MMP-13 reactivity was also observed in capillaries of normal human skin.
  • Cultured human dermal microvascular endothelial cells and human umbilical vein endothelial cells expressed MMP-13 mRNA and protein.
  • MMP-13 expression was upregulated by IL-1alpha, TNF-alpha, and PMA, with IL-1alpha being the most potent inducer.
  • Enzyme expression was further enhanced in endothelial cells grown on 3D collagen lattices compared to collagen films.

Conclusions:

  • Endothelial cells in the skin are a significant source of MMP-13.
  • MMP-13 expression in endothelial cells is upregulated by inflammatory cytokines and growth factors, suggesting a role in angiogenesis and vascular differentiation.
  • These findings highlight MMP-13 as a potential target in conditions involving tumor angiogenesis.

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