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PMID: 21251905 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Consistent interactions between tumor cell IL-6 and macrophage TNF-α enhance the growth of human prostate cancer cells in the bone of nude mouse.

International immunopharmacology ·Vol. 11 ·No. 7 ·2011-07-00 ·Pages 862-72

Kim SW, Kim JS, Papadopoulos J, Choi HJ, He J, Maya M, Langley RR, Fan D, Fidler IJ, Kim SJ

Abstract

To test the hypothesis that tumor-associated macrophages (TAMs) enhance the growth and metastasis of human prostate cancer in the bone, we evaluated the effects of decreasing interleukin-6 (IL-6) production by tumor cells and TAMs in a mouse model of bone metastasis. Human PC-3MM2 cells that produce IL-6 were transfected with lentivirus containing IL-6 small hairpin RNA (shRNA) or nonspecific RNA and injected into the tibias of nude mice treated intraperitoneally every 5days for 5weeks with phosphate-buffered saline (PBS), liposomes containing PBS, or liposomes containing clodronate (to decrease the number of macrophages). Transfection of PC-3MM2 cells with IL-6 shRNA significantly decreased cellular expression of IL-6 and the number of TAMs and osteoclasts in bone tumors, which correlated with significant decreases in tumor size, bone lysis, and incidence of lymph node metastasis. Treatment of mice with clodronate liposomes significantly decreased the number of TAMs and osteoclasts in the bone tumors, the expression of IL-6 in the PC3-MM2 cells, and the production of tumor necrosis factor (TNF)-α by TAMs. These findings correlated with a significant decrease in tumor size, bone lysis, and lymph node metastasis. Knocking down IL-6 in tumor cells and decreasing TAMs was associated with the lowest incidences of bone tumors and lymph node metastasis. These results suggest that TAMs enhance the growth of prostate cancer cells in the bone.

MeSH Terms
Animals Bone Neoplasms/immunology,secondary Carcinoma/immunology,secondary Cell Communication/drug effects,genetics,immunology Cell Line, Tumor Clodronic Acid/administration & dosage,metabolism Humans Interleukin-6/genetics,immunology,metabolism Liposomes/metabolism Macrophages/drug effects,immunology,metabolism,pathology Male Mice Mice, Nude Osteoclasts/immunology,metabolism,pathology Prostatic Neoplasms/immunology,pathology RNA, Small Interfering/genetics Tumor Burden/drug effects,genetics Tumor Necrosis Factor-alpha/immunology,metabolism
Chemicals
Interleukin-6 Liposomes RNA, Small Interfering Tumor Necrosis Factor-alpha Clodronic Acid
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Kim Seung Wook
Department of Cancer Biology, Cancer Metastasis Research Center, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Kim Jang Seong
Papadopoulos John
Choi Hyun Jin
He Junqin
Maya Marva
Langley Robert R
Fan Dominic
Fidler Isaiah J
Kim Sun-Jin
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Article Info
Journal
International immunopharmacology
Abbr.
Int Immunopharmacol
ISSN
1878-1705
DOI
10.1016/j.intimp.2011.01.004
Published
2011-07-00
Epub
2011-00-18
Pages
862-72
Language
English
Region
Netherlands
NLM ID
100965259
PMCID
PMC3086935
Subset
IM
Grants
NCI NIH HHS · P30 CA016672 · United States
NCI NIH HHS · CA16672 · United States
NCI NIH HHS · U54 CA143837 · United States
NCI NIH HHS · 1U54-CA143837 · United States
NCI NIH HHS · U54 CA143837-04 · United States
NCI NIH HHS · P30 CA016672-36 · United States
External Links
PubMed source DOI: 10.1016/j.intimp.2011.01.004 PMC Full Text View journal details
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