BONE-MARROW FIBROBLASTIC PROGENITORS IN PATIENTS WITH ADVANCED BREAST-CANCER

Bone marrow fibroblast colony-forming cells (CFU-F) were studied in fi fteen consecutive untreated breast cancer patients (BCP) with clinical stages III and IV, and in sixteen normal controls (NC). A decreased n umber of CFU-F was observed in BCP compared to NC (p < 0.004). Conflue nce of the adherent cell layer was observed in all normal bone marrow mononuclear cells (MC) cultures, while a lower proportion of cultures from BCP (11/15) showed confluent adherent cell layers. When MC cultur es of BCP were treated with indomethacin (Indo, 10(-6)M) 50% of them i ncreased the number of CFU-F compared to the value obtained without tr eatment. In addition, a significant increase in the release of PGE2 in BCP cultures was observed before Indo treatment. Moreover, after MC w ere fractionated into adherent and non-adherent progenitors, the CFU-F decreased in both types of fractions of BCP compared to NC value (p < 0.02 and < 0.05, respectively). The number of light density MC per 10 mi of bone marrow aspirate and the number of trypsin-sensitive adhere nt progenitors were lower than NC in BCP (p < 0.02 and 0.013, respecti vely). Total MC and fibroblasts (fourth passage) were cultivated to ev aluate the production of interleukin-1 beta (IL-1 beta) by ELISA metho dology. Results indicated no difference of IL-1 beta spontaneous relea se when total MC cultures of both groups were compared. However, the l evels of this cytokine were lower (<10 pg/ml) in fibroblast culture su pernatants of BCP compared to NC (1,217 +/- 74 pg/ml). Fibroblast cult ures from BCP showed low or no release of IL-1 beta after muramyl-dipe ptide (MDP, 1 mu g/ml) stimulation. In conclusion, the defective proli ferative and confluence capacity of BCP fibroblastic progenitors may b e related to the decrease in the production of IL-1 beta by these prec ursors.