Influences of stroma-derived growth factors on the cytokine expression pattern of human breast cancer cell lines.

Tumor growth and local invasion are greatly dependent on the malignant potential of a tumor cell, but are also significantly modulated by a variety of local factors. These factors comprise cytokines, growth factors and extracellular matrix proteins (ECM), which act through a complex system of auto-, para- and juxtacrine interactions. Some factors are produced by the malignant cell itself, others are expressed by adjacent tumor stroma, migrated inflammatory cells, or resident macrophages. We have investigated the influences of cytokines and growth factors known to be expressed by tumor stroma on the cytokine expression pattern of three human breast cancer cell lines of different malignant potential. MCF-7, T47D and MDA-MB-231 were incubated with human recombinant TNF-alpha, IGF-I, IGF-II, bFGF, HGF or G-CSF and the pattern of tumor-cell-derived TGF-beta1, bFGF, IL-1alpha and VEGF was analyzed. Among the three cell lines used we observed a heterogenous response to stromal cytokines by measuring above mentioned factors in the cell culture's supernatants, but no clear correlation between malignant potential and cytokine expression pattern seemed obvious. We hypothesize that local growth factors may have a significant modulatory effect on malignant behavior in vivo. We conclude that this effect might depend on individual responses and on the differentiation state of tumor cells.