Correlation between metastatic potential and variants from colorectal tumor cell line HT-29.
OBJECTIVE
To evaluate the relationship between uPA, PAI-1, CEA, PI3K and metastatic potential in three colorectal tumor cell lines.


METHODS
Metastatic model in nude rats was established by variants HT-29c and HT-29d cell lines and the metastatic potential of two tumor cell variants was compared. Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) were determined using ELISA in colorectal carcinoma WiDr, HT-29 and HT-29d cell lines with different metastatic potentials. Expression of carcinoembryonic antigen (CEA) and phosphoinositide 3-kinase (PI3-Kinase) was analyzed using immunohistochemistry (IHC) in these cell lines in vitro and in vivo. CEA expression was compared using fluorescence activated cell sorter (FACS) in vitro.


RESULTS
The number of HT-29d cells arrested in liver dramatically decreased within the initial 24 hours after injection. The taking rate of liver metastases in the variant HT-29d increased as compared with parental HT-29 cells (70% versus 50%) and a variant HT-29b cells (70% versus 60%), and extensive organs were synchronously involved in metastases. The uPA concentration of variant HT-29d cell line was significantly higher than that of the non-metastatic WiDr and the low metastatic HT-29 cell lines. The variant HT-29d cells produced stronger PI3-kinase expression as compared with the non-metastatic WiDr cells and the low metastatic HT-29 cells in vivo.


CONCLUSIONS
The selected variant HT-29d cell exhibited an enhanced metastatic potential. The level of uPA and PAI-1 is positively correlated with the metastatic capacity of tumor cells. The expression of PI3-kinase correlates with tumor development and metastasis.
Wang
Min
M
Department of Surgical Oncology, First Affiliated Hospital of Medical College, Zhejiang University, Hangzhou 310003, Zhejiang Province, China. pfeng@mail.hz.zj.cn
Vogel
Ilka
I
Kalthoff
Holger
H
D000230:Adenocarcinoma / Q000556:secondary*; D000818:Animals; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D045744:Cell Line, Tumor / Q000378:metabolism / Q000637:transplantation; D015179:Colorectal Neoplasms / Q000556:secondary*; D004195:Disease Models, Animal; D008297:Male; D009368:Neoplasm Transplantation; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D051381:Rats; D011923:Rats, Nude; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D002272:Carcinoembryonic Antigen; D017395:Plasminogen Activator Inhibitor 1; D019869:Phosphatidylinositol 3-Kinases; D014568:Urokinase-Type Plasminogen Activator