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
Autor: | Isaiah J. Fidler, Jang Seong Kim, John Papadopoulos, Dominic Fan, Sun Jin Kim, Junqin He, Robert R. Langley, Seung Wook Kim, Marva Maya, Hyun Jin Choi |
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Jazyk: | angličtina |
Rok vydání: | 2011 |
Předmět: |
Male
Pathology medicine.medical_specialty medicine.medical_treatment Immunology Mice Nude Osteoclasts Bone Neoplasms Cell Communication Article Metastasis Small hairpin RNA Prostate cancer Mice Nude mouse Cell Line Tumor Immunology and Allergy Medicine Animals Humans RNA Small Interfering Pharmacology biology business.industry Interleukin-6 Tumor Necrosis Factor-alpha Macrophages Carcinoma Bone metastasis Prostatic Neoplasms medicine.disease biology.organism_classification Tumor Burden Cytokine Cancer cell Liposomes Cancer research Tumor necrosis factor alpha Clodronic Acid business |
Zdroj: | Scopus-Elsevier |
Popis: | 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 5 days for 5 weeks 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. |
Databáze: | OpenAIRE |
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