Circulating tumor cells (CTCs) were first described 150 years ago. The so-called "classical" CTC populations (EpCAM+/CK+/CD45-) have been fully characterized and proposed as the most representative CTC subset, with clinical relevance. Nonetheless, other "atypical" or "unconventional" CTCs have also been identified, and their critical role in metastasis formation was demonstrated. In this chapter we illustrate the studies that led to the discovery of unconventional CTCs, defined as CTCs that display both epithelial and mesenchymal markers, or both cancer and immune markers, also in the form of hybrid cancer-immune cells. We also present biological explanations for the origin of these unconventional CTCs: epithelial to mesenchymal transition, cell-cell fusion and trogocytosis. We believe that a deeper knowledge on the biology of CTCs is needed to fully elucidate their role in cancer progression and their use as cancer biomarkers.

中文翻译：

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解决非常规循环肿瘤细胞的不确定性：上皮间质转化、细胞融合和吞噬作用。

循环肿瘤细胞 (CTC) 于 150 年前首次被描述。所谓的“经典”CTC 群体 (EpCAM+/CK+/CD45-) 已得到充分表征，并被提议为最具代表性的 CTC 子集，具有临床相关性。尽管如此，其他“非典型”或“非常规”CTC 也已被发现，并证明了它们在转移形成中的关键作用。在本章中，我们将阐述导致非常规 CTC 发现的研究，这些 CTC 被定义为同时显示上皮和间质标记物，或同时显示癌症和免疫标记物的 CTC，也以混合癌症免疫细胞的形式存在。我们还对这些非常规 CTC 的起源提出了生物学解释：上皮到间质的转变、细胞间融合和吞噬作用。我们认为，需要对 CTC 的生物学有更深入的了解，才能充分阐明它们在癌症进展中的作用以及它们作为癌症生物标志物的用途。