Tumor-derived CCL5 does not contribute to breast cancer progression.
Besides functioning as a chemotactic factor, CCL5 has been associated with progression of disease in women with breast cancer, immune modulation and metastasis. Here we asked whether CCL5 produced by tumor cells contributed to growth or metastasis of breast cancer. For this purpose, we used two murine mammary carcinomas, the 4T1 tumor which is metastatic and constitutively expresses CCL5, and the 168 tumor which is not metastatic and does not constitutively express CCL5. RNA interference was used to inhibit CCL5 expression from the 4T1 tumor, and a CCL5 transgene was used to express CCL5 by the 168 tumor. Six different clones of 4T1 that exhibited stable reduction in CCL5 expression, and three different clones of 168 that exhibited stable CCL5 expression were compared to the parental tumors and vector transfected controls. Significantly, in both models, tumor-derived CCL5 expression did not correlate with MHC expression, growth rate, or metastatic ability of the tumors. These results show that tumor-derived CCL5 expression alone does not make a significant contribution to breast cancer progression.
Jayasinghe
Mevan M
MM
Department Biology, Lafayette College, Easton, PA 18042, USA.
Golden
Jacqueline M
JM
Nair
Priyanka
P
O'Donnell
Cara M
CM
Werner
Michael T
MT
Kurt
Robert A
RA
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006649:Histocompatibility Antigens / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D006649:Histocompatibility Antigens; D034741:RNA, Small Interfering