转移是造成大多数癌症相关死亡的原因。我们之前确定了导致转移事件的特定癌细胞群，这些细胞群在管腔肿瘤中为细胞角蛋白-14 (CK14) 和 E-钙粘蛋白阳性，在三阴性肿瘤中为 E-钙粘蛋白和波形蛋白阳性。由于癌细胞在由免疫细胞和基质细胞组成的复杂生态系统中进化，我们试图破译这些侵袭性癌细胞群在肿瘤微环境（TME）内的空间相互作用。我们使用成像质谱流式细胞术检测肿瘤微阵列中的 36 种蛋白质，其中包含来自腔内或三阴性乳腺癌 (TNBC) 的成对原发性和转移性病变，从而产生包含 1,477,337 个注释细胞的数据集。着眼于转移起始细胞群，我们观察到与特定成纤维细胞和巨噬细胞亚型非常接近，这是原发性肿瘤和转移性肿瘤之间维持的关系。值得注意的是，管腔癌细胞中的高 CK14 和 TNBC 细胞中的高波形蛋白与特定巨噬细胞亚型（CD163intCD206intPDL1intHLA-DR 或 PDL1highARG1high）密切相关。我们深入的空间分析表明，转移起始癌细胞始终与 TME 内的不同细胞群共定位，表明这些细胞间相互作用在促进转移中发挥着作用。© 2024。作者，获得 Springer 独家许可自然有限公司。

Metastasis is responsible for the majority of cancer-related fatalities. We previously identified specific cancer cell populations responsible for metastatic events which are cytokeratin-14 (CK14) and E-cadherin positive in luminal tumors, and E-cadherin and vimentin positive in triple-negative tumors. Since cancer cells evolve within a complex ecosystem comprised of immune cells and stromal cells, we sought to decipher the spatial interactions of these aggressive cancer cell populations within the tumor microenvironment (TME). We used imaging mass cytometry to detect 36 proteins in tumor microarrays containing paired primary and metastatic lesions from luminal or triple-negative breast cancers (TNBC), resulting in a dataset of 1,477,337 annotated cells. Focusing on metastasis-initiating cell populations, we observed close proximity to specific fibroblast and macrophage subtypes, a relationship maintained between primary and metastatic tumors. Notably, high CK14 in luminal cancer cells and high vimentin in TNBC cells correlated with close proximity to specific macrophage subtypes (CD163intCD206intPDL1intHLA-DR+ or PDL1highARG1high). Our in-depth spatial analysis demonstrates that metastasis-initiating cancer cells consistently colocalizes with distinct cell populations within the TME, suggesting a role for these cell-cell interactions in promoting metastasis.© 2024. The Author(s), under exclusive licence to Springer Nature Limited.