Honegger A E, Hofer E L, Barañao R I, Mackinlay T A, Mackinlay D A, Bullorsky E O, Bordenave R H, Chasseing N A
Instituto de Biología y Medicina Experimental, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina.
Ann Hematol. 2002 Feb;81(2):80-5. doi: 10.1007/s00277-001-0410-y. Epub 2002 Jan 18.
We analyzed the ability of the bone marrow (BM) stromal cells to achieve confluence and their proliferative capacity in BM primary cultures from 30 untreated lung cancer patients (LCP), 27 breast cancer patients (BCP), and 30 normal controls (NC) when these confluent cells were induced to proliferate following four continuous subcultures. Moreover, we evaluated the production of interleukin-1 beta (IL-1beta), transforming growth factor beta 1 (TGF-beta1), fibronectin, and prostaglandin E2 (PGE2) by pure fibroblasts (fourth passage). A fibroblast colony-forming units (CFU-F) assay was used to investigate the proliferative and confluence capacity. Levels of IL-1beta, TGF-beta1, and fibronectin in conditioned mediums (CM) of fibroblast cultures were measured by enzyme-linked immunosorbent assay (ELISA) kit and PGE(2) by radioimmunoassay (RIA) kit. Confluence was achieved in the 60% of LCP and 78% of BCP primary cultures compared with 100% of NC, and only fibroblasts from seven LCP and six BCP cultures had the capacity to proliferate following four subcultures. Levels of IL-1beta were below 10 pg/ml in both patient groups, while NC had a mean value of 5882.57+/-221.61 pg/ml. Levels of TGF-beta1 in BCP were lower than NC values ( P<0.05). LCP and BCP had significantly decreased levels of fibronectin when compared to NC values ( P<0.05 and P<0.01, respectively). Levels of PGE2 in LCP were higher compared to NC ( P<0.01). In conclusion, BM fibroblasts from LCP and BCP presented a defective proliferative and confluence capacity, and this deficiency may be associated with the alteration of IL-1beta, TGF-beta1, fibronectin, and PGE2 production.
我们分析了来自30例未经治疗的肺癌患者（LCP）、27例乳腺癌患者（BCP）和30例正常对照（NC）的骨髓（BM）原代培养物中骨髓基质细胞达到汇合的能力及其增殖能力，这些汇合细胞在连续传代四次后被诱导增殖。此外，我们评估了纯成纤维细胞（第四代）产生白细胞介素-1β（IL-1β）、转化生长因子β1（TGF-β1）、纤连蛋白和前列腺素E2（PGE2）的情况。采用成纤维细胞集落形成单位（CFU-F）试验来研究增殖和汇合能力。通过酶联免疫吸附测定（ELISA）试剂盒测量成纤维细胞培养条件培养基（CM）中IL-1β、TGF-β1和纤连蛋白的水平，通过放射免疫测定（RIA）试剂盒测量PGE2的水平。与100%的NC相比，LCP原代培养物中有60%达到汇合，BCP原代培养物中有78%达到汇合，只有来自7例LCP和6例BCP培养物的成纤维细胞在传代四次后具有增殖能力。两个患者组中IL-1β水平均低于10 pg/ml，而NC的平均值为5882.57±221.61 pg/ml。BCP中TGF-β1水平低于NC值（P<0.05）。与NC值相比，LCP和BCP的纤连蛋白水平显著降低（分别为P<0.05和P<0.01）。LCP中PGE2水平高于NC（P<0.01）。总之，LCP和BCP的BM成纤维细胞呈现出增殖和汇合能力缺陷，这种缺陷可能与IL-1β、TGF-β1、纤连蛋白和PGE2产生的改变有关。
