Lipopolysacchride-treated mammary carcinomas secrete proinflammatory chemokines and exhibit reduced growth rates in vivo, but not in vitro.
Toll-like receptors (TLR) are pattern recognition receptors that play a pivotal role in the initiation of immune responses. Here we report that the murine mammary carcinoma 4T1 constitutively expressed genes encoding TLR2, 3, 4 and 5. Moreover, treatment of the 4T1 cell line with peptidoglycan (PGN), polyinosinic-polycytidylic acid (Poly(I:C)) or lipopolysaccharide (LPS), agonists for TLR2, 3 or 4 respectively, induced nuclear translocation of NFkappaB and secretion of CCL2, CCL5 and CXCL1 in a dose dependent manner. Although treating the tumor cells with the TLR agonists did not modulate growth or viability of the tumor cells in vitro, 4T1 exhibited a decreased growth rate in vivo following treatment with LPS that was dependent upon the presence of CD8(+) T cells. Analysis of 3 additional murine mammary carcinomas revealed that they also secreted CCL2, CCL5 and CXCL1 in response to TLR agonist treatment, and LPS treated 168 and SM1 tumors exhibited decreased growth rates in vivo, but not in vitro. These data indicated that 4 out of 4 murine mammary carcinomas secreted proinflammatory chemokines following treatment with TLR agonists, and 3 out of 4 of the mammary carcinomas responded to LPS treatment in a manner that decreased tumor growth in vivo.
Nair
P
P
Department of Biology, Lafayette College, Easton, PA 18042, USA.
O'Donnell
C M
CM
Janasek
K
K
Sajduk
M K
MK
Smith
E A
EA
Golden
J M
JM
Vasta
C A
CA
Huggins
A B
AB
Kurt
Robert A
RA
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D018925:Chemokines / Q000276:immunology / Q000378:metabolism*; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008212:Lymphocyte Depletion; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism*; D010457:Peptidoglycan / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D051193:Toll-Like Receptors / Q000819:agonists
D018925:Chemokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010457:Peptidoglycan; D051193:Toll-Like Receptors; D011070:Poly I-C