近日，意大利欧洲肿瘤学研究所Gioacchino Natoli等研究人员合作发现，功能与形态变异的映射揭示了胰腺癌区域细胞外基质破坏和神经侵袭的基础。相关论文于2024年3月21日在线发表于国际学术期刊《癌细胞》。

为了阐明支撑胰腺导管腺癌（PDAC）瘤内形态变异的基因表达程序，研究人员在单细胞水平上对组织学上不同的PDAC细胞簇的分子图谱进行了研究和去卷积。研究人员发现了三种主要的形态和功能变异，它们以不同的比例共存于所有PDAC中，显示出有限的遗传多样性，并与细胞外基质的独特组织相关联。

一种具有经典导管特征的腺变异；一种显示中止导管结构和混合内胚层及肌成纤维细胞样基因表达的过渡变异；以及一种缺乏导管特征和基底膜的分化不良变异，并显示出神经元谱系的初始化。体内外证据证明，这些变体之间存在动态转变，部分受细胞外基质成分和硬度的影响，并与局部（特别是神经）侵袭有关。

据悉，PDAC的瘤内形态异质性可预测临床预后，但在分子水平上却只有部分了解。

附：英文原文

Title: Mapping functional to morphological variation reveals the basis of regional extracellular matrix subversion and nerve invasion in pancreatic cancer

Author: Pierluigi Di Chiaro, Lucia Nacci, Fabiana Arco, Stefania Brandini, Sara Polletti, Andrea Palamidessi, Benedetta Donati, Chiara Soriani, Francesco Gualdrini, Gianmaria Frigè, Luca Mazzarella, Alessia Ciarrocchi, Alessandro Zerbi, Paola Spaggiari, Giorgio Scita, Simona Rodighiero, Iros Barozzi, Giuseppe R. Diaferia, Gioacchino Natoli

Issue&Volume: 2024-03-21

Abstract: Intratumor morphological heterogeneity of pancreatic ductal adenocarcinoma (PDAC)predicts clinical outcomes but is only partially understood at the molecular level.To elucidate the gene expression programs underpinning intratumor morphological variationin PDAC, we investigated and deconvoluted at single cell level the molecular profilesof histologically distinct clusters of PDAC cells. We identified three major morphologicaland functional variants that co-exist in varying proportions in all PDACs, displaylimited genetic diversity, and are associated with a distinct organization of theextracellular matrix: a glandular variant with classical ductal features; a transitionalvariant displaying abortive ductal structures and mixed endodermal and myofibroblast-likegene expression; and a poorly differentiated variant lacking ductal features and basementmembrane, and showing neuronal lineage priming. Ex vivo and in vitro evidence supports the occurrence of dynamic transitions among these variants in partinfluenced by extracellular matrix composition and stiffness and associated with local,specifically neural, invasion.

DOI: 10.1016/j.ccell.2024.02.017

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(24)00079-5