The CXCR5 chemokine receptor is expressed by carcinoma cells and promotes growth of colon carcinoma in the liver.
The chemokine receptor CXCR5 is expressed by B cells and certain T cells and controls their migration into and within lymph nodes. Its ligand BCA-1/CXCL13 is present in lymph nodes and spleen and also in the liver. Surprisingly, we detected CXCR5 in several mouse and human carcinoma cell lines. CXCR5 was particularly prominent in pancreatic carcinoma cell lines and was also detected by immunohistochemistry in 7 of 18 human pancreatic carcinoma tissues. Expression in CT26 colon carcinoma was low in vitro, up-regulated in vivo, and rapidly lost when cells were explanted in vitro. CXCL13 strongly promoted proliferation of CXCR5-transfected CT26 cells in vitro. In the liver, after intrasplenic injection, these CXCR5 transfectants initially grew faster than controls, but the growth rate of control tumors accelerated later to become similar to the transfectants, likely due to the up-regulation of CXCR5. Inhibition of CXCR5 function, by trapping CXCR5 in the endoplasmic reticulum using a CXCL13-KDEL "intrakine," had no effect on initial growth of liver foci but later caused a prolonged growth arrest. In contrast, s.c. and lung tumors of CXCR5- and intrakine-transfected cells grew at similar rates as controls. We conclude that expression of CXCR5 on tumor cells promotes the growth of tumor cells in the liver and, at least for CT26 cells, seems to be required for outgrowth to large liver tumors. Given the limited expression on normal cells, CXCR5 may constitute an attractive target for therapy, particularly for pancreatic carcinoma.
Meijer
Joost
J
Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Zeelenberg
Ingrid S
IS
Sipos
Bence
B
Roos
Ed
E
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D000818:Animals; D045744:Cell Line, Tumor / Q000737:chemistry / Q000637:transplantation; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000008:administration & dosage / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016503:Drug Delivery Systems; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000008:administration & dosage; D009928:Organ Specificity; D010190:Pancreatic Neoplasms / Q000737:chemistry; D021382:Protein Sorting Signals; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013154:Spleen; D013160:Splenic Neoplasms / Q000556:secondary; D014162:Transfection
C110663:CXCL13 protein, human; C095085:CXCR5 protein, human; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; D009363:Neoplasm Proteins; D009842:Oligopeptides; D021382:Protein Sorting Signals; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D011993:Recombinant Fusion Proteins; C073762:lysyl-aspartyl-glutamyl-leucine