TY - JOUR
T1 - Requirement for specific proteases in cancer cell intravasation as revealed by a novel semiquantitative PCR-based assay
AU - Kim, J.
AU - Yu, W.
AU - Kovalski, K.
AU - Ossowski, L.
N1 - Funding Information:
The project was supported by the Guidance Foundation, the Sanya Institute of Nanjing Agricultural University (NAUSY-MS06), the National Key Project for Jiangsu Agriculture Science and Technology Innovation Fund (CX(2019)1008), and grants from the National Key Research and Development Program of China (2020YFE0202900), the Natural Science Foundation of China (32072033, 31871602, 31171516), the Natural Science Foundation of Jiangsu Province (BK20211212), and the Fundamental Research Funds for the Central Universities (KYZZ2022003).
PY - 1998/8/7
Y1 - 1998/8/7
N2 - Proteases are crucial for cancer metastasis, but due to lack of assays, their role in intravasation has not yet been tested. We have developed a human Alu sequence PCR-based assay to quantitate intravasated cells in an in vivo model. We demonstrated that metalloproteinases (MMPs), and most likely MMP-9, are required for intravasation by showing that marimastat, an inhibitor of MMPs, reduced intravasation by more than 90%, and that only tumor cell lines expressing MMP-9 intravasated. Cells with low surface urokinase plasminogen activator (uPA) and uPA receptor (uPAR) were also incapable of intravasation, despite the presence of high levels of MMP-9. We concluded that breaching of the vascular wall is a rate-limiting step for intravasation, and consequently for metastasis, and that cooperation between uPA/uPAR and MMP-9 is required to complete this step.
AB - Proteases are crucial for cancer metastasis, but due to lack of assays, their role in intravasation has not yet been tested. We have developed a human Alu sequence PCR-based assay to quantitate intravasated cells in an in vivo model. We demonstrated that metalloproteinases (MMPs), and most likely MMP-9, are required for intravasation by showing that marimastat, an inhibitor of MMPs, reduced intravasation by more than 90%, and that only tumor cell lines expressing MMP-9 intravasated. Cells with low surface urokinase plasminogen activator (uPA) and uPA receptor (uPAR) were also incapable of intravasation, despite the presence of high levels of MMP-9. We concluded that breaching of the vascular wall is a rate-limiting step for intravasation, and consequently for metastasis, and that cooperation between uPA/uPAR and MMP-9 is required to complete this step.
UR - http://www.scopus.com/inward/record.url?scp=0032493871&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(00)81478-6
DO - 10.1016/S0092-8674(00)81478-6
M3 - Article
C2 - 9708737
AN - SCOPUS:0032493871
SN - 0092-8674
VL - 94
SP - 353
EP - 362
JO - Cell
JF - Cell
IS - 3
ER -