Chonnam Med J.  2003 Dec;39(4):218-222.

Pathophysiological Role of Vascular Endothelial Growth Factor (VEGF) and Matrix Metalloproteinases (MMP) in Metastatic Brain Tumor-associated Intracerebral Hemorrhage

• Ahn KY
• Shin BA
• Choi C
• Rhu HH
• Jeong YI
• Sun HS
• Jung TY
• Kim IY
• Lee MC
• Jung S

Abstract

Cerebrovascular complications can develop in a variety of tumor-related conditions. Intratumoral hemorrhage occurs principally in malignant brain tumors. Overexpression of vascular endothelial growth factor (VEGF) and metalloproteinase (MMP) in addition to being associated with tumor development and metastasis, cause tumor-associated intracerebral hemorrhage in an experimental system. As VEGF and MMP in metastatic brain tumors may play a significant role in tumor-associated hemorrhage, we investigated the potential role of VEGF and MMP in causing metastatic brain tumor-associated bleeding. Their expressions were determined by immunohistochemistry in pathological specimens of metastatic brain tumors obtained from 16 patients. We also examined the expression of collagen type IV, CD34, Factor VIII in respect to the status of tumor vasculature. Seven patients had hemorrhage in the tumor and the other 9 patients had no intratumoral bleeding. There was higher VEGF expression with neovascularization in the hemorrhagic metastatic tumors than in the non-hemorrhagic tumors. The basement membranes of newly formed vessels were disrupted in cases of highly expressing MMP-2 and MMP-9 among the metastatic brain tumors studied. These data indicate that rapid growing nascent blood vessels, responding vigorously to VEGF, are concentrated around the hemorrhagic tumors. Additionally, the basement membranes of these fragile vessels could be disrupted proteolytically by MMP. We conclude that verexpression of VEGF and MMP may play a role in metastatic brain tumor-associated hemorrhage. Presumably, the underlying pathophysiological mechanisms are rapid growth and breakdown of vessels around the tumors, caused by cells overexpressing VEGF and MMP.

Keyword

Metastastic Cancer; Brain; Tumor Bleeding; VEGF; MMP

MeSH Terms

Basement Membrane
Blood Vessels
Brain Neoplasms
Brain*
Cerebral Hemorrhage*
Collagen Type IV
Factor VIII
Hemorrhage
Humans
Immunohistochemistry
Matrix Metalloproteinases*
Neoplasm Metastasis
Vascular Endothelial Growth Factor A*
Collagen Type IV
Factor VIII
Matrix Metalloproteinases
Vascular Endothelial Growth Factor A