Possible pathophysiological role of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in metastatic brain tumor-associated intracerebral hemorrhage.
BACKGROUND
Intratumoral hemorrhage, as one of the cerebrovascular complications in various tumor-related conditions, occurs mainly in malignant brain tumors. Recent studies have shown that the overexpression of vascular endothelial growth factor (VEGF) and metalloproteinase (MMP) may play a role for the loss of vascular integrity and the subsequent hemorrhage in several instances, in addition to their well-known properties in tumor development and metastasis.


METHODS
To investigate the potential role of VEGF and MMP in hemorrhagic complication of metastatic brain tumor, we estimated the expression of VEGF, MMP-2 & -9 by immunohistochemical studies in pathological specimens of metastatic brain tumors obtained from 16 patients, 7 in hemorrhagic and 9 in non-hemorrhagic group. We also examined the expression of collagen type IV, CD34, Factor VIII in order to evaluate the status of tumor vasculature.


RESULTS
Patients in hemorrhagic group showed a higher VEGF expression with neovascularization than those in non-hemorrhagic group. The basement membranes of newly formed vessels were disrupted in cases with high expression in both MMP-2 and -9. These results indicate that rapid growing nascent blood vessels, responding vigorously to VEGF, are concentrated around the hemorrhagic tumors. Besides, these results suggest a possibility that the basement membranes of these nascent vessels could be disrupted proteolytically by MMP.


CONCLUSIONS
We conclude that overexpression of VEGF and MMP may play a role in metastatic brain tumor-associated hemorrhage. Presumably, the underlying pathophysiological mechanisms are through rapid growth and breakdown of vessels around the tumors caused by overexpression of VEGF and MMP of tumor cells.
Jung
Shin
S
Department of Neurosurgery, Chonnam National University Hwasun Hospital & Medical School, Gwangju, Republic of Korea. sjung@chonnam.ac.kr
Moon
Kyung-Sub
KS
Jung
Tae-Young
TY
Kim
In-Young
IY
Lee
Young-Hwa
YH
Rhu
Hyang-Hwa
HH
Sun
Heung-Suk
HS
Jeong
Young-Il
YI
Kim
Kyung-Keun
KK
Kang
Sam-Suk
SS
D000368:Aged; D001932:Brain Neoplasms / Q000098:blood supply / Q000150:complications* / Q000556:secondary; D002543:Cerebral Hemorrhage / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D042461:Vascular Endothelial Growth Factor A; D020782:Matrix Metalloproteinases