Tumor cells gain advantages in growth and survival by acquiring genotypic and phenotypic heterogeneity. Interactions with bystander cells in the tumor microenvironment contribute to the progression of heterogeneity. We have shown that fusion between tumor and bystander cells is one form of interaction, and that tumor–bystander cell fusion has contrasting effects. By trapping fusion hybrids in the heterokaryon or synkaryon state, tumor–bystander cell fusion prevents the progression of heterogeneity. However, if trapping fails, fusion hybrids will resume replication to form derivative clones with diverse genomic makeups and behavioral phenotypes. To determine the characteristics of bystander cells that influence the fate of fusion hybrids, we co-cultured prostate mesenchymal stromal cell lines and their spontaneously transformed sublines with LNCaP as well as HPE-15 prostate cancer cells. Subclones derived from cancer–stromal fusion hybrids were examined for genotypic and phenotypic diversifications. Both stromal cell lines were capable of fusing with cancer cells, but only fusion hybrids with the transformed stromal subline generated large numbers of derivative subclones. Each subclone had distinct cell morphologies and growth behaviors and was detected with complete genomic hybridization. The health conditions of the bystander cell compartment play a crucial role in the progression of tumor cell heterogeneity.
肿瘤细胞通过获得基因型和表型异质性，在生长和存活中获得优势。与肿瘤微环境中旁观者细胞的相互作用促进了异质性的进展。我们已证明肿瘤细胞与旁观者细胞的融合是相互作用的一种形式，且肿瘤-旁观者细胞融合具有双重效应。通过将融合杂合体捕获在异核或合核状态，肿瘤-旁观者细胞融合可阻止异质性的进展。然而，若捕获失败，融合杂合体将恢复复制，形成具有不同基因组构成和行为表型的衍生克隆。为确定影响融合杂合体命运的旁观者细胞特征，我们将前列腺间充质基质细胞系及其自发转化亚系与LNCaP及HPE-15前列腺癌细胞共培养。对源自癌-基质融合杂合体的亚克隆进行基因型和表型多样性分析。两种基质细胞系均能与癌细胞融合，但仅与转化基质亚系的融合杂合体能产生大量衍生亚克隆。每个亚克隆均具有独特的细胞形态和生长行为，并通过完整基因组杂交技术检测确认。旁观者细胞区室的状态对肿瘤细胞异质性的进展起着至关重要的作用。
肿瘤(癌症)患者之家