TY  - JOUR
TI  - The countercurrent principle in invasion and metastasis of cancer cells. Recent insights on the roles of chemokines

AU  - Opdenakker, Ghislain
AU  - Van-Damme, Jo
T2  - The International Journal of Developmental Biology
AB  - Chemokine production by cancer cells constitutes a duality. Leukocyte 
recruitment under the pressure of chemokines may be beneficial for the host or for the tumor. Here, the 
emphasis will be on the detrimental effects of chemokines in tumor biology. A decade ago, the 
countercurrent principle of tumor-derived chemokine and peritumoral protease production was formulated 
to explain chemokine expression as a selective advantage for specific tumors and as a phenotype 
of invasive and metastasizing cancer cells. Chemoattracted leukocytes may provide trophic 
factors and produce invasion and metastasis-promoting proteinases. On the basis of the 
consensus sequence glutamic acid-leucine-arginine (ELR) preceding the canonical cysteine-any amino 
acid-cysteine (CXC), ELR-positive CXC chemokines, such as interleukin-8 and granulocyte 
chemotactic protein-2, are angiogenic and thus instruct the host to feed the tumor and bring the vessels into closer contact with the tumor cells. These mechanisms may enhance lymphogenic and 
hematogenic metastasis. Recent research and proofs of this countercurrent concept are here reviewed and compared. In addition, we discuss how alterations in chemokine ligand and receptor 
expression profiles may contribute to tumor growth, invasion, metastasis and immune evasion. 
These comparisons imply practical consequences for future cancer diagnosis and therapy. The 
implications include methods to diminish metastasis by inhibiting angiogenic CXC chemokine ligands 
and receptors, therapeutic combinations of chemokine overexpression with antigenic stimuli and 
co-treatment with angiostatic chemokines and tumor antigens. 

PY  - 2004
DO  - 10.1387/ijdb.041796go
VL  - 48
IS  - 5-6
SP  - 519
EP  - 527
J2  - Int. J. Dev. Biol.
LA  - en
SN  - 0214-6282
SN  - 1696-3547
UR  - https://ijdb.ehu.eus/article/041796go
Y2  - 2024/11/05/15:23:26
ER  -