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Production of Growth Factors by Human Myeloma Cells

Unité de recherches d'Immunopathologie, INSERM U291, Zolad, rue Puech Villa, 34100 Montpellier, Cédex [B. K., M. J., R. B.], and INSERM U131, Hôpital A. Béclére, 32 rue des Carnets, 92140 Clamart [A. V., B. D.]

Using in vitro-growing myeloma cell lines, we studied the growth factors involved in human multiple myeloma, and particularly the potential of autocrine secretion and response to B-cell growth factor (BCGF) of RPMI 8226, the best-documented Epstein-Barr virus-negative human myeloma cell line. We found that three myeloma cell lines (RPMI 8226, U266, and IM9) produce an autostimulatory growth factor (AGF) and thus increase their own proliferation by 2- to 3-fold in cells cultured at low density. Optimal AGF production was obtained after 24 h of culture at a cell density ranging from 2.5 to 5 million cells/ml. The three myeloma cell lines produce type II BCGF, able to induce the proliferation of highly purified human peripheral blood B-cells, only after anti-µ activation. The BCGF produced by RPMI 8226 can be adsorbed onto RPMI 8226 cells together with the RPMI 8226 AGF, and the two are copurified on gel filtration in a peak with an apparent molecular weight of 70,000. RPMI 8226 can be efficiently activated by human high molecular weight BCGF II (M_r 50,000) and less extensively by BCGF I (M_r 12,000). RPMI 8226 does not produce either detectable ILI or interferons and and IL1 and -IFN had no stimulating effect on RPMI 8226 proliferation. Our findings support the conclusion that RPMI 8226 produces a BCGF II working as an AGF.

¹ Supported by grants from the Association pour la Recherche sur le Cancer, Paris, France.

² To whom requests for reprints should be addressed.

Received 2/27/87. Revised 5/22/87. Accepted 6/24/87.

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