Blood monocytes stimulate migration of human pancreatic carcinoma cells in vitro: the role of tumour necrosis factor - alpha.
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-alpha (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.
Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, ul. Gronostajowa 7, 30-387 Kraków, Poland.
Bartłomiej
B
Baran
Iga
I
Bechyne
Maciej
M
Siedlar
Katarzyna
K
Szpak
Bozenna
B
Mytar
Jolanta
J
Sroka
Eliza
E
Laczna
Zbigniew
Z
Madeja
Marek
M
Zembala
Jarosław
J
Czyz
D002450:Cell Communication / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000494:pharmacology
D014409:Tumor Necrosis Factor-alpha