Author(s): Gerharz CD, Reinecke P, Schneider EM, Schmitz M, Gabbert HE
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Abstract OBJECTIVES: To analyze the secretion of hematopoietic growth factors and the expression of their corresponding receptors in 40 newly established renal cell carcinoma (RCC) cell lines of different histologic types. Little is known about the secretion and function of hematopoietic growth factors by human RCCs. METHODS: The expression of the hematopoietic growth factors (ie, erythropoietin, interleukin [IL]-3, IL-5, granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], and macrophage colony-stimulating factor [M-CSF]) was determined by enzyme-linked immunosorbent assay analysis under different culture conditions, including suspension culture and monolayer cultures (plastic and Matrigel-coated culture flasks). The expression of their corresponding receptors was defined by fluorescence activated cell scanner analysis and by reverse-transcriptase polymerase chain reaction. The response of the RCC cell lines to exogenous hematopoietic growth factors was analyzed by MTT assay. RESULTS: In almost all of the cell lines, significant amounts of GM-CSF and M-CSF were secreted, and in four cell lines, a secretion of G-CSF was detected. Fourteen RCC cell lines showed secretion of IL-3, and production of IL-5 and erythropoietin was not observed in any cell line. Secretion of GM-CSF and M-CSF was affected by the substratum offered for cell attachment in the adherent cultures. GM-CSF secretion was more pronounced under culture conditions with a reduced frequency of cell-to-cell contacts. Two cell lines were shown to express receptors for M-CSF, but receptors for G-CSF and GM-CSF could not be detected in any cell line. Exposure to exogenous G-CSF, GM-CSF, and M-CSF did not affect the proliferation of our RCC cell lines. CONCLUSIONS: The results of our study clearly demonstrate that human RCC cells can secrete significant amounts of G-CSF, GM-CSF, M-CSF, and IL-3, and are thereby theoretically able to modulate the host's tumor-directed immune response.
This article was published in Urology
and referenced in Journal of Thyroid Disorders & Therapy