Blood monocytes stimulate migration of human pancreatic carcinoma cells in vitro: The role of tumour necrosis factor – alpha

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• 作者：BartŁ ; omiej Baran ; Iga Bechyne ; Maciej Siedlar ; Katarzyna Szpak ; Boż ; enna Mytar ; Jolanta Sroka ; Eliza ł ; aczna ; Zbigniew Madeja ; Marek Zembala ; JarosŁ ; aw Czyż
• 关键词：Cancer ; Monocytes ; TNF ; Cell motility ; Tumour invasion
• 刊名：European Journal of Cell Biology
• 出版年：2009
• 出版时间：December 2009
• 年：2009
• 卷：88
• 期：12
• 页码：743-752
• 全文大小：445 K

文摘

In some types of cancers, tumour-infiltrating monocytes/macrophages (TIM) may be responsible for the formation of an invasive microenvironment in a manner dependent on the secretion of soluble mediators such as tumour necrosis factor-α (TNF). Human pancreatic carcinoma (HPC-4) cells are able to induce TNF production by monocytes. Here, the effect of human peripheral blood monocytes, precursors of TIM, on the motility of co-cultured HPC-4 cells, was directly analysed in vitro. A phenotypic transition, i.e., the appearance of rear-front polarised HPC-4 cells paralleled by their increased motility, and increased motility of monocytes, were observed. This effect was attenuated when HPC-4 cells and monocytes were co-cultured in the presence of inhibitors of TNF production and anti-TNF monoclonal antibodies, indicating the specific role of this cytokine in determining paracrine loops between monocytes and cancer cells. Moreover, exogenous TNF induced HPC-4 cell motility concomitantly to the appearance of cellular features characteristic for epithelial-mesenchymal transition (EMT) such as rear-front polarisation, rearrangements of the actin cytoskeleton characteristic for motile cells and the induction of Snail-1 expression. Since cell movement is crucial for cancer invasion and the formation of metastases, these findings demonstrate an EMT-dependent mechanism of cancer progression which acts through the phenotypic transition of pancreatic cancer cells dependent on monocyte-derived TNF.