Invasion Front-specific Overexpression of Tissue Inhibitor of Metalloproteinase-1 in Liver Metastases from Colorectal Cancer
Background: Matrix metalloproteinases (MMPs) and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), have been implicated in invasion and metastasis. The distribution of MMPs and TIMPs in the invasion front of liver metastases from colorectal cancer were investigated in order to u...
Saved in:
Published in | Anticancer research Vol. 28; no. 3A; pp. 1459 - 1465 |
---|---|
Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Attiki
International Institute of Anticancer Research
01.05.2008
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Background: Matrix metalloproteinases (MMPs) and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), have
been implicated in invasion and metastasis. The distribution of MMPs and TIMPs in the invasion front of liver metastases from
colorectal cancer were investigated in order to understand their potential role in invasiveness. Materials and Methods: Freshly
frozen material of colorectal metastases of the liver was microdissected into four separate compartments, namely pure liver,
liver invasion, tumour invasion and pure tumour. RNA was isolated and analyzed on Affymetrix microarrays. Expression of TIMP-1
was confirmed by quantitative polymerase chain reaction in 10 colorectal liver metastases. Cellular localisation of TIMP-1
was examined by immunohistochemistry. Results: Affymetrix microarray data revealed that several MMP and TIMP genes including
MMP-2, -3, -7, -9, -11, -12, -14, -15, -16, -19 and -24, and TIMP-1, -2 and -3 were generally up-regulated in both invasion
front compartments. Among these genes, TIMP-1 showed the highest expression. The qPCR results indicated an average 15-fold
up-regulation of TIMP-1 in the liver invasive front and an average 13-fold up-regulation in the tumor invasive front, each
compared to normal liver tissue. Immunohistochemistry revealed expression of TIMP-1 in tumour epithelia as well as in host
tissue cells, including fibroblastic cells. Conclusion: Our data indicate that tumour invasion in colorectal liver metastasis
is associated with increased TIMP-1 RNA and protein levels in both tumour and host cells. |
---|---|
Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0250-7005 1791-7530 |