|
  |
| |
|
| |
Expression
of Matrix Metalloprotease-9 in Vascular Pericytes in Human Breast Cancer
|
|
|
Boye Schnack
Nielsen, Maxwell Sehested, Lars Kjeldsen, Niels Borregaard, J\orgen Rygaard,
and Keld Dano |
| |
|
| |
Department
of Pathology (BSN, MS), Finsen Laboratory (BSN, KD), and Granulocyte Research
Laboratory (LK, NB), Rigshospitalet, and Bartholin Institute (JR), Kommunehospitalet,
Copenhagen, Denmark |
| |
|
| |
Matrix metalloprotease-9
(MMP-9; 92-kd type IV collagenase, gelatinase B) is regarded as important
for degradation of the basement membrane and extracellular matrix during
cancer invasion and other tissue-remodeling events. Expression of MMP-9
was analyzed in 22 cases of human ductal breast cancer by immunohistochemistry
and in 8 of these cases also by in situ hybridization. For immunohistochemistry
we used affinity-purified polyclonal antibodies as well as a MMP-9-specific
monoclonal antibody (clone 6-6B). Three different stromal cell types with
a positive MMP-9 immunoreaction were identified morphologically: neutrophils
and macrophage-like cells in all cases and vascular cells in 16 of 22 cases.
Double immunofluorescence with antibodies to CD68 conclusively demonstrated
MMP-9 expression in macrophages. To identify the positive vascular cells,
we employed antibodies to von Willebrand factor and PAL-E for identification
of endothelial cells, high molecular weight melanoma-associated antigen
for pericytes, and alpha-smooth muscle actin for vascular smooth muscle
cells. Using conventional and confocal double immunofluorescence microscopy,
colocalization of MMP-9 was seen with high molecular weight melanoma-associated
antigen, the pericyte marker, whereas little or no coexpression was seen
with alpha-smooth muscle actin. Virtually no coexpression was seen with
the endothelial cell markers PAL-E and von Willebrand factor. In situ hybridization
showed that MMP-9 mRNA colocalized with MMP-9 immunoreactivity in macrophages
and vascular structures, whereas no MMP-9 mRNA was detected in neutrophils.
No MMP-9 immunostaining or in situ hybridization signal was detected in
cancer cells in any of the cases. Based on these results, it is concluded
that MMP-9 in human breast cancer is located in tumor-infiltrating stromal
cells, including neutrophils, macrophages, and vascular pericytes, and that
the latter two cell types also produce this metalloprotease. We suggest
that the MMP-9 produced in pericytes may play a role i extracellular matrix
degradation during tumor angiogenesis. |
| |
|
| |
 |
