Extracellular matrix proteins modulate cytokine production by monocytes during their interactions with cancer cells.

Background: This study examined the role of extracellular matrix compounds (EMC) in the alteration of tumour necrosis factor-alpha (TNFalpha) and interleukin-10 (IL-10) production by human monocytes stimulated with cancer cells. Materials and Methods: Monocytes were cultured with cancer cells in the absence or presence of EMC and cytokine release was measured by ELISA. In some experiments monocytes preincubated with monoclonal antibodies (mAbs) against CD29 and CD44 were used. Results: Fibronectin, collagen type I and type IV induced production of cytokines by monocytes and mAbs inhibited this effect. The release of TNFalpha by moncytes stimulated with cancer cells was inhibited by fibronectin.. collagen type I and IV and IL-10 by fibronectin and collagen type IV. Other EMC were ineffective. Both mAbs partly reversed this inhibitory effect. Conclusion: These findings suggest that some EMC induce cytokine release by monocytes but inhibit monocyte-cancer cell interactions and this effect is presumably due to competition for the same receptors.