Chemokine receptors in interactions of monocytes with tumour cells


Kaczmarczyk, Grzegorz


gangliosides ; chemokine receptors ; monocytes ; tumour cells


Monocytes/rnacrophages play an important role in the host antiturnour response. Monocytes are precursors of tumour infiltrating macrophages and may be affected by tumour cell products both in the blood and in the tumour microenvironrnent. The aim of the study was to evaluate the expression of receptors for some chernokines on monocytes during their interactions with turnour cells. The expression of chernokine receptors: CCRI, CCR2, CCR5, CXCR4 on monocytes was determined after their contact with pancreatic cancer cells (HPC-4 line) and neuroblastorna cells (CHP-100 line), exposure to supematants from their culture, and gangliosides which are shed by turnour cells. The expression of chemokine receptors was evaluated at the surface, intracellular protein, and transcription levels. Furthermore, the effect of gangliosides on the migration of monocytes to chemokines such as MIP-la, MCP-2, SDF-1, the production of cytokines (TNFa, IL-10, IL-12), chemokines and ROI by monocytes stimulated with tumour cells were evaluated. The data suggest that the decrease of chemokine receptors (CCRI, CCR5, CXCR4) on monocytes after their contact with tu.m our cells is induced by tumour cells products - gangliosides and/or chemokines. Gangliosides, mainly GT1b and GM2, inhibited CCRI, CCR5 and CXCR4 expression on monocytes and their migration to MIP-la and SDF-1. The mRNA for ch ; emokine receptors was not altered by gangliosides, but the CXCR4 cytoplasmic expression was increased. Gangliosides exerted an inhibitory effect on cytokine secretion (TNFa, IL-10, IL-12), but did not inhibit the production of ROI as well as MIP-la secretion, by monocytes stimulated with tumour cells. Hence gangliosides and chemokines significantly modify biologica! activity of monocytes and hence antitumour response of the host.

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Level of degree:

2 - studia doktoranckie

Degree discipline:

immunologia ; biologia molekularna

Degree grantor:

Wydział Lekarski


Zembala, Marek



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Praca doktorska

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