FIBROBLASTIC COLONY-FORMING-UNITS AND LEVELS OF TUMOR-NECROSIS-FACTORAND PROSTAGLANDIN-E2 IN BONE-MARROW CULTURES FROM PATIENTS WITH ADVANCED LUNG-CARCINOMA

BACKGROUND, Although alterations of the bone marrow (BM) fibroblast co lony-forming cells are involved in the development of diverse hematolo gic disorders, these progenitors still have not been well characterize d in patients with solid tumors. METHODS, The incidence of fibroblast colony-forming units (CFU-F) was evaluated in the cultures of unsepara ted and fractionated light density BM mononuclear cells (MC) from 25 c onsecutive untreated lung carcinoma patients (LCP) and 16 normal contr ols (NC). Unseparated MC also were cultured in the presence of indomet hacin (10(-6) M). Finally, the authors evaluated the spontaneous produ ction of prostaglandin E2 (PGE2) and tumor necrosis factor-alpha (TNF- alpha) in culture conditioned mediums of unseparated MC by radioimmuno assay and enzyme-linked immunoadsorbent assay methodology, respectivel y. RESULTS, A decreased number of CFU-F was observed in unseparated an d fractionated (adherent and nonadherent) light density MC cultures fr om LCP compared with NC. When unseparated MC of LCP were treated with indomethacin, a slightly increase in the number of CFU-F was found. Ad herent MC (stromal cells) achieved confluence only in 44% of LCP prima ry cultures compared with 100% of NC. Overproduction of PGE2 and TNF-a lpha was found in the conditioned mediums of LCP compared with the mea n values obtained in NC (P < 0.05 and P < 0.02, respectively). CONCLUS IONS, The lack of confluence and suppression of CFU-F in BM of LCP may be related to the increase production of PGE2 and TNF-alpha. Future i nvestigation will allow the determination of how these modifications i nfluence tumor cell growth and will prove if more alterations of the h ematopoietic microenvironment imply a worse prognosis. (C) 1997 Americ an Cancer Society.