芬兰赫尔辛基大学Sara A. Wickström团队近期取得重要工作进展，他们通过研究多参数成像，揭示了头颈癌临床相关的癌细胞-间质相互作用动力学。相关研究成果2024年10月28日在线发表于《细胞》杂志上。

据介绍，上皮性肿瘤的特点是肿瘤间和肿瘤内存在丰富的异质性，这使诊断和治疗变得复杂。癌症与基质之间的相互作用对这种异质性的贡献尚不清楚。

研究人员报告了一种用单细胞分辨率量化头颈部鳞状细胞癌（HNSCC）表型多样性的范式。通过将细胞状态标记与形态学特征相结合，研究人员确定了与临床特征相关的表型特征，包括转移和复发。

肿瘤和间质特征的整合表明，部分上皮间质转化（pEMT）使疾病结果对间质成分高度敏感，从而产生强烈的预后和预测特征。

癌症球体动力学的空间转录组学和随后的分析，确定了癌症相关的成纤维细胞-pEMT轴，是将pEMT细胞重新编程为侵袭表型的细胞间信号传导的联系。

总之，这一研究建立了一种范式来识别临床相关的肿瘤表型，并发现基质和上皮区室之间的细胞状态依赖性相互作用，这种相互作用驱动癌症侵袭。

附：英文原文

Title: Multiparameter imaging reveals clinically relevant cancer cell-stroma interaction dynamics in head and neck cancer

Author: Karolina Punovuori, Fabien Bertillot, Yekaterina A. Miroshnikova, Mirjam I. Binner, Satu-Marja Myllymki, Gautier Follain, Kai Kruse, Johannes Routila, Teemu Huusko, Teijo Pellinen, Jaana Hagstrm, Noemi Kedei, Sami Ventel, Antti Mkitie, Johanna Ivaska, Sara A. Wickstrm

Issue&Volume: 2024-10-28

Abstract: Epithelial tumors are characterized by abundant inter- and intra-tumor heterogeneity, which complicates diagnostics and treatment. The contribution of cancer-stroma interactions to this heterogeneity is poorly understood. Here, we report a paradigm to quantify phenotypic diversity in head and neck squamous cell carcinoma (HNSCC) with single-cell resolution. By combining cell-state markers with morphological features, we identify phenotypic signatures that correlate with clinical features, including metastasis and recurrence. Integration of tumor and stromal signatures reveals that partial epithelial-mesenchymal transition (pEMT) renders disease outcome highly sensitive to stromal composition, generating a strong prognostic and predictive signature. Spatial transcriptomics and subsequent analyses of cancer spheroid dynamics identify the cancer-associated fibroblast-pEMT axis as a nexus for intercompartmental signaling that reprograms pEMT cells into an invasive phenotype. Taken together, we establish a paradigm to identify clinically relevant tumor phenotypes and discover a cell-state-dependent interplay between stromal and epithelial compartments that drives cancer aggression.

DOI: 10.1016/j.cell.2024.09.046

Source: https://www.cell.com/cell/abstract/S0092-8674(24)01146-2