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Human monocytes and proinflammatory cytokines stimulate breast and prostate cancer cell invasion
Author(s) -
Lindholm Paul Franklin,
Lu Yi,
Jovanovic Borko D,
Sivapurapu Neela,
Lee Chung
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.470.9
Subject(s) - monocyte , chemokine , cancer research , prostate cancer , cancer cell , cell culture , proinflammatory cytokine , cancer , du145 , cell , biology , matrigel , immunology , inflammation , angiogenesis , lncap , biochemistry , genetics
The objective of this study is to determine how monocyte/macrophages stimulate cancer cell growth and invasion. Co‐cultures with freshly isolated human monocytes or monocytoid cell lines stimulated invasion of several breast and prostate cancer cell lines. The co‐cultures produced high levels of IL‐6 and IL‐8 and increased MCP‐1 and Gro‐α chemokines above cancer cell or monocyte culture supernatants alone. Addition of purified recombinant interleukin‐8 and MCP‐1 proteins stimulated monocyte and cancer cell chemotaxis in Matrigel‐coated Transwell chambers. The co‐cultures also stimulated cancer cell NF‐κB reporter activity and nuclear localization. The co‐culture induced cancer cell invasion was blocked by biochemical inhibitors or dominant negative expression of IκBα or RhoA N19 mutants that inhibited NF‐κB activity. These studies indicate that human breast and prostate cancer cells cross‐communicate with monocytoid cells to stimulate cancer cell invasion in a NF‐κB dependent manner. This model has potential to identify treatments that block monocyte/macrophage‐induced cancer cell invasion and progression. Supported by Prostate S.P.O.RE. P50CA90386 and CDMRP DAMD‐17‐02‐1‐0162.