Analysis of the mechanisms in multiple myeloma cell growth----Paracrine, Autocrine and Factor-independent Growth----

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The growth mechanisms of multipje myeloma cells were studied utilizing ten estabhshed human multiple myeloma cell lines and molecular biological methods.1. Ten human multiple myeloma cell lines were established using macrophages as a feeder layer. Four of them were derived from bone marrow and the other 6 from extrarnedullary lesions.2. Bone marrow-derived ceU. 1ines grew dependently on a macrophage feeder layer or in response to interleuldn-6(IL-6). In contrast, extrameduffary lesion-derived cell lines grew independent of any feeder layers or cytokines.3. All cell lines constitutively expressed IL-6 receptor (IL-6R) mRNA and cell surface IL-6R.4. All cell lines except for AMO1 prolfferated in response to IL-6. Bone marrow-derived cell lines proliferated absolutely dependently on IL-6. Spontaneously proliferating extramedullary-lesion derived cell lines additively proliferated in response to IL-6.5. No cell lines constitutively expressed IL-6 mRNA nor secreted IL-6.6. The anti-IL-6 antibody or anti-IL-6R antibody inhibited only IL-6-induced proliferation, but did not inhibit the spontaneous proliferation of extramedullary lesion-derived cell lines.These results indicate that the IL-6 paracrine mechanism plays the central role in the growth of bone marrow-derived cell lines. In contrast, the factor-independent mechanism plays a primary role in the growth of extra meduffary lesion-derived cell lines, that also additively proliferate in response to IL-6 (paracrine mechanisms). Because no IL-6 mRNA was detected in any cell lines, the intracellular autocrine mechanism or autocrine mechanisim appeared not to be operating in any of the cell lines.