Role of CXCR4 and SDF-1 in mammary tumor metastasis in the cat.
It has recently been suggested that the chemokine receptor CXCR4 and its ligand SDF-1 (CXCL12) promote metastasis of various cancers in humans. Since feline mammary tumors also metastasize to distant organs frequently, we used real-time quantitative PCR to examine the expression of feline CXCR4 (fCXCR4) in ten feline mammary tumor cell lines and seven feline mammary tumor tissues, and also the expression of feline SDF-1 (fSDF-1) in various organs. Cell lines derived from metastatic regions expressed more fCXCR4 than those derived from primary tumors. Mammary tumor tissues overexpressed more fCXCR4 than normal mammary tissues. Organs with high levels of fSDF-1 expression represent common sites of metastasis. Migration assays using the feline mammary tumor cell line NAC were also performed to test the activity of TN14003 and TC14012, antagonists of human CXCR4, to antagonize fCXCR4 expressed on NAC cells. TN14003 and TC14012 inhibited migration of NAC cells. We conclude that fCXCR4 may be a therapeutic target for feline mammary tumors.
Laboratory of Veterinary Physiology, Faculty of Agriculture, Iwate University, Morioka, Japan.
Toshina
T
Oonuma
Masami
M
Morimatsu
Takayuki
T
Nakagawa
Rina
R
Uyama
Nobuo
N
Sasaki
Munekazu
M
Nakaichi
Hirokazu
H
Tamamura
Nobutaka
N
Fujii
Shizu
S
Hashimoto
Hozumi
H
Yamamura
Bunei
B
Syuto
D000818:Animals; D002415:Cats; D002460:Cell Line; D002465:Cell Movement; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics / Q000502:physiology; D002633:Chemotaxis / Q000502:physiology; D017931:DNA Primers; D005260:Female; D015674:Mammary Neoplasms, Animal / Q000473:pathology* / Q000503:physiopathology; D009362:Neoplasm Metastasis / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D019718:Receptors, CXCR4 / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D017931:DNA Primers; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D011994:Recombinant Proteins