PO.TB10.12 · 肿瘤生物学

生长缓慢、预后不良的结直肠癌中一种驱动基质重塑与CAF募集的癌细胞内在程序

A cancer cell intrinsic program for matrix remodeling and CAF recruitment in slow growing, poor prognosis colorectal cancers

编号 776 展板 21 时间 4/19 02:00–05:00 区域 Section 31 主讲 Claudio Isella, PhD

分会场 Physicochemical Modulation of Cancer Ecosystems: Mechanical Forces, Hypoxia, and Acidosis

该海报暂无可下载的资料 AACR 官方页面

作者与单位 Authors & Affiliations

Claudio Isella¹, Anna Cassisa¹, Consalvo Petti², Alexandra Ambra Ulla¹, Jie Zhou³, Carlo Leonardi¹, Roberta Porporato¹, Daniela Cantarella¹, Letizia Franco², Cinzia Benetti¹, Jill Carol Rubinstein⁴, Jessica Erriquez², Mariangela Russo⁵, Francesco Sassi², Elena Grassi², Ymera Pignochino⁶, Alberto Puliafito², Ivan Molineris¹, Rebecca Senetta⁷, Andrea Bertotti⁸, Livio Trusolino⁹, Jeffrey H. Chuang¹⁰, Alberto Bardelli¹¹, Enzo Medico¹²

¹Università degli Studi di Torino, Torino, Italy,²Institute for Cancer Research and Treatment, Candiolo, Italy,³The Jackson Laboratory for Genomic Medicine, Farmington, CT,⁴The Jackson Laboratory for Genomic Medicine, Bridgeport, CT,⁵IRCC - Institute for Cancer Research and Treatment, Institute for Cancer Research and Treatment, Candiolo, Italy,⁶Junior Group Leader, Dept of Oncology, Institute for Cancer Research and Treatment, Candiolo, Italy,⁷University of Turin, Turin, Italy,⁸Asst. Professor, Dept. of Oncological Sci., University of Turin, Candiolo (TO), Italy,⁹Fondazione del Piemonte per l'Oncologia, Candiolo, Italy,¹⁰The Jackson Laboratory, Farmington, CT,¹¹IFOM Istituto Fondazione di Oncologia Molecolare ETS, Milan, Italy,¹²Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy

摘要 Abstract

中文摘要

为探究癌细胞的分子程序如何塑造其与肿瘤微环境的相互作用，我们由19株人结直肠癌（CRC）细胞系构建了小鼠异种移植瘤，并进行RNA测序，分别对人源（癌）和鼠源（基质）转录组进行分析。各细胞系的异种移植瘤生长速率差异显著，并与基质丰度相关：生长较慢的肿瘤积累了更多基质。这些富含基质、生长缓慢的肿瘤中的癌细胞表现出一种协同的转录程序，涉及上皮-间质转化（EMT）和细胞外基质（ECM）重塑，我们将其命名为EMT-基质重塑（EMR）特征。相应的基质成纤维细胞表现出以基质重塑相关癌相关成纤维细胞（mrCAF）特征所定义的基质重塑活性。整合人CRC的批量、单细胞和空间转录组学数据，证实了EMR癌细胞与mrCAF的共现及空间邻近，二者均与不良临床结局相关。泛癌分析揭示，EMR和mrCAF特征在多种肿瘤类型中反复出现，且同样标志着侵袭性疾病。总之，这些发现揭示了一种由癌-基质相互作用驱动的ECM重塑的保守机制：具有EMT样、基质重塑表型的癌细胞募集并指导CAF重塑肿瘤微环境，从而促进肿瘤进展。

查看英文原文 English abstract

To investigate how the molecular programs of cancer cells shape their crosstalk with the tumor microenvironment, we generated mouse xenografts from 19 human colorectal cancer (CRC) cell lines and performed RNA sequencing, separately profiling human (cancer) and murine (stromal) transcriptomes. Xenograft growth rates varied markedly across lines and correlated with stromal abundance: slower-growing tumors accumulated more stroma. Cancer cells from these stroma-rich, slow tumors displayed a coordinated transcriptional program involving epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) remodeling, which we termed the EMT-Matrix Remodeling (EMR) signature. The corresponding stromal fibroblasts exhibited matrix-remodeling activity defined by a matrix-remodeling cancer-associated fibroblast (mrCAF) signature. Integration of human CRC bulk, single-cell, and spatial transcriptomics confirmed the co-occurrence and spatial proximity of EMR cancer cells and mrCAFs, both associated with adverse clinical outcome. A pan-cancer analysis revealed that EMR and mrCAF signatures recur across multiple tumor types, where they similarly mark aggressive disease. Collectively, these findings uncover a conserved mechanism of ECM remodeling driven by reciprocal cancer-stromal interactions: cancer cells with an EMT-like, matrix-remodeling phenotype recruit and instruct CAFs to reshape the tumor microenvironment, thereby promoting tumor progression.

利益披露 Disclosure

C. Isella, None.. A. Cassisa, None.. A. A. Ulla, None.. C. Leonardi, None.. R. Porporato, None.. D. Cantarella, None.. C. Benetti, None.. I. Molineris, None.

← 返回 AACR 2026 检索