Perinucleolar compartment prevalence is a phenotypic pancancer marker of malignancy.
Perinucleolar compartment prevalence is a phenotypic pancancer marker of malignancy.
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作者：
Norton JT;Pollock CB;Wang C;Schink JC;Kim JJ;Huang S
核仁周室（PNC）是位于核仁外围的亚核结构。以前使用乳腺癌作为模型系统的研究表明，PNC患病率（具有1个或多个PNC的细胞百分比）随着疾病进展而增加，并与患者预后不良相关。为了评价PNC患病率作为一种新的泛癌预后标志物的有效性，作者研究了PNC患病率是否与一系列组织类型中的恶性肿瘤相关，并在各种实验条件下评价了其与恶性肿瘤的选择性相关性。PNC患病率低的原代和永生化细胞和细胞系来源于血液恶性肿瘤，但它是异质性的细胞系来源于实体瘤，包括上皮和非上皮来源。使用人子宫肌层组织和具有不同恶性程度的甲状腺癌细胞系进行的研究证明了高PNC患病率与恶性潜能之间的相关性。此外，PNC患病率直接对应于一系列充分表征的相同来源的细胞系中的转移能力，所述细胞系在小鼠模型中针对不同水平的转移能力进行选择。相反，PNC患病率降低实验过度表达乳腺癌细胞中的抗转移蛋白。然而，PNC患病率与癌症和正常细胞共有的特征无关，包括增殖，糖酵解和分化。总之，这些观察结果有助于验证PNC患病率选择性地代表广泛的实体组织肿瘤中的恶性肿瘤，证明其有可能被开发为恶性肿瘤的泛癌预后标志物。
The perinucleolar compartment (PNC) is a subnuclear structure localized at the nucleolar periphery. Previous studies using breast cancer as a model system demonstrated that PNC prevalence (the percentage of cells with 1 or more PNC) increased with disease progression and was associated with poor patient outcomes. To evaluate the validity of developing PNC prevalence as a novel pan-cancer prognostic marker, the authors investigated whether PNC prevalence was correlated with malignancy in a spectrum of tissue types and evaluated its selective association with malignancy under various experimental conditions. PNC prevalence was low in primary and immortalized cells and in cell lines derived from hematologic malignancies, but it was heterogeneous in cell lines derived from solid tumors, including those of epithelial and nonepithelial origins. Studies using human myometrial tissue and thyroid cancer cell lines with various levels of malignancy demonstrated a correlation between high PNC prevalence and malignant potential. Furthermore, PNC prevalence corresponded directly to metastatic capacities in a series of well characterized cell lines of the same origin that were selected for various levels of metastatic capacity in a mouse model. Conversely, PNC prevalence was reduced experimentally by over expressing an antimetastatic protein in breast cancer cells. However, PNC prevalence was not associated with traits that were shared by both cancer and normal cells, including proliferation, glycolysis, and differentiation. Together, these observations helped to verify that PNC prevalence selectively represents malignancy in a broad spectrum of solid tissue tumors, demonstrating its potential to be developed as a pancancer prognostic marker of malignancy.