Albright C D, Jones R T, Hudson E A, Fontana J A, Trump B F, Resau J H
Department of Pathology, University of Maryland School of Medicine, Baltimore 21201.
Cell Biol Toxicol. 1990 Oct;6(4):379-98. doi: 10.1007/BF00120804.
Normal human bronchial epithelial cells (BE) and adenovirus-12 SV40 hybrid virus transformed, non-tumorigenic human bronchial epithelial cells (BEAS-2B) were cultured for 7 days in a serum-free hormone supplemented medium. BE cells after 3 days in culture were exposed to conditioned medium (CMt) from confluent BEAS-2B cells. By day 7, CMt-treated BE cells exhibited a lower colony forming efficiency (CFE), fewer cells per colony, and a reduced mitotic index (MI) and BrdU (bromodeoxyuridine) labeling index. CMt also enhanced the expression of a terminally differentiated squamous phenotype in BE cells. Cell free lysates from BEAS-2B cells (CFLt) had effects similar to CMt on the MI and morphology of BE cells. In contrast, CMt and CFLt did not inhibit the growth, or alter the morphology of BEAS-2B cells. Conditioned medium from BE cells (CMn) did not reduce the growth of BEAS-2B cells, and had little effect on the morphology of BE cells. In co-cultures, BE cells in direct contact with BEAS-2B cells had a lower MI (0.4-0.7 vs. 1.6%) compared with colonies of BE cells in these cocultures. The concentration of transforming growth factor beta (TGF-beta) in conditioned media from BEAS-2B cells (CMt) was increased 10-fold over that in CMn. TGF-beta is known to induce terminal differentiation in epithelial cells. These results suggest that the selective growth advantage of transformed cells over normal cells during human bronchial carcinogenesis may be related to the release of autocrine/paracrine factors (e.g., TGF-beta) from transformed cells, which down-regulates and terminally differentiates the normal cells.
将正常人支气管上皮细胞（BE）和经腺病毒12 - SV40杂交病毒转化的、无致瘤性的人支气管上皮细胞（BEAS - 2B）在补充了血清和激素的无血清培养基中培养7天。培养3天后的BE细胞暴露于来自汇合的BEAS - 2B细胞的条件培养基（CMt）中。到第7天时，经CMt处理的BE细胞表现出较低的集落形成效率（CFE）、每个集落中的细胞数量减少、有丝分裂指数（MI）降低以及溴脱氧尿苷（BrdU）标记指数降低。CMt还增强了BE细胞中终末分化鳞状表型的表达。来自BEAS - 2B细胞的无细胞裂解物（CFLt）对BE细胞的MI和形态具有与CMt相似的作用。相比之下，CMt和CFLt不抑制BEAS - 2B细胞的生长，也不改变其形态。来自BE细胞的条件培养基（CMn）不降低BEAS - 2B细胞的生长，并且对BE细胞的形态影响很小。在共培养中，与这些共培养中的BE细胞集落相比，与BEAS - 2B细胞直接接触的BE细胞具有较低的MI（0.4 - 0.7%对1.6%）。来自BEAS - 2B细胞的条件培养基（CMt）中转化生长因子β（TGF - β）的浓度比CMn中的增加了10倍。已知TGF - β可诱导上皮细胞终末分化。这些结果表明，在人类支气管癌发生过程中，转化细胞相对于正常细胞的选择性生长优势可能与转化细胞释放自分泌/旁分泌因子（例如TGF - β）有关，这些因子下调并使正常细胞终末分化。
