Bone marrow fibroblastic progenitors in patients with advanced breast cancer

Bone marrow fibroblast colony-forming cells (CFU-F) were studiedin fifteen consecutive untreated breast cancer patients (BCP)with clinical stages III and IV, and insixteen normal controls (NC). A decreased number ofCFU-F was observed in BCP compared to NC(p < 0.004). Confluence of the adherent celllayer was observed in all normal bone marrowmononuclear cells (MC) cultures, while a lower proportionof cultures from BCP (11/15) showed confluent adherentcell layers. When MC cultures of BCP weretreated with indomethacin (Indo, 10^-6M) 50% of themincreased the number of CFU-F compared to thevalue obtained without treatment. In addition, a significantincrease in the release of PGE2 in BCPcultures was observed before Indo treatment. Moreover, afterMC were fractionated into adherent and non-adherent progenitors,the CFU-F decreased in both types of fractionsof BCP compared to NC value (p <0.02 and < 0.05, respectively). The number oflight density MC per 10 ml of bonemarrow aspirate and the number of trypsin-sensitive adherentprogenitors were lower than NC in BCP (p< 0.02 and 0.013, respectively). Total MC andfibroblasts (fourth passage) were cultivated to evaluate theproduction of interleukin-1 (IL-1) by ELISA methodology. Resultsindicated no difference of IL-1 spontaneous release whentotal MC cultures of both groups were compared.However, the levels of this cytokine were lower(< 10 pg/ml) in fibroblast culture supernatants ofBCP compared to NC (1,217 ± 74 pg/ml).Fibroblast cultures from BCP showed low or norelease of IL-1 after muramyl-dipeptide (MDP, 1 µg/ml)stimulation. In conclusion, the defective proliferative and confluencecapacity of BCP fibroblastic progenitors may be relatedto the decrease in the production of IL-1by these precursors.