Bone marrow fibroblastic progenitors in patients with advanced breast cancer.
Bone marrow fibroblast colony-forming cells (CFU-F) were studied in fifteen consecutive untreated breast cancer patients (BCP) with clinical stages III and IV, and in sixteen normal controls (NC). A decreased number of CFU-F was observed in BCP compared to NC (p < 0.004). Confluence 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 cultures of BCP were treated with indomethacin (Indo, 10(-6)M) 50% of them increased the number of CFU-F compared to the value obtained without treatment. In addition, a significant increase in the release of PGE2 in BCP cultures was observed before Indo treatment. Moreover, after MC were 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 ml of bone marrow aspirate and the number of trypsin-sensitive adherent progenitors were lower than NC in BCP (p < 0.02 and 0.013, respectively). Total MC and fibroblasts (fourth passage) were cultivated to evaluate the production of interleukin-1 beta (IL-1 beta) by ELISA methodology. Results indicated no difference of IL 1 beta spontaneous release when total MC cultures of both groups were compared. However, the levels of this cytokine were lower (< 10 pg/ml) in fibroblast culture supernatants of BCP compared to NC (1,217 +/- 74 pg/ml). Fibroblast cultures from BCP showed low or no release of IL-1 beta after muramyl-dipeptide (MDP. 1 microgram/ml) stimulation. In conclusion, the defective proliferative and confluence capacity of BCP fibroblastic progenitors may be related to the decrease in the production of IL-1 beta by these precursors.
Chasseing
N A
NA
Instituto de Biología Medicina Experimental, Buenos Aires, Argentina.
Trejo
Y G
YG
Bordenave
R H
RH
Bullorsky
E O
EO
Diaz
N B
NB
Rumi
L S
LS
D001707:Biopsy, Needle; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology*; D001940:Breast / Q000166:cytology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000378:metabolism; D013234:Stem Cells / Q000473:pathology
D007375:Interleukin-1; D015232:Dinoprostone