Circulating tumor cells (CTCs) that survive in the blood are playing an important role in the metastasis process of tumor. In addition, they have become a tool for tumor diagnosis, prognosis and recurrence monitoring. CTCs can exist in the blood as individual cells or as clumps of aggregated cells. In recent years, more and more studies have shown that clustered CTCs have stronger metastasis ability compared to single CTCs. With the deepening of studies, scholars have found that cancer cells can combine not only with each other, but also with non-tumor cells present in the blood, such as neutrophils, platelets, etc. At the same time, it was confirmed that non-tumor cells bound to CTCs maintain the survival and proliferation of cancer cells through a variety of ways, thus promoting the occurrence and development of tumor. In this review, we collected information on tumorigenesis induced by CTC clusters to make a summary and a discussion about them. Although CTC clusters have recently been considered as a key role in the transition process, many characteristics of them remain to be deeply explored. A detailed understanding of their vulnerability can prospectively pave the way for new inhibitors for metastasis.

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Circulating tumor cell (CTC) clusters runs a critical role in carcinoma metastasis. However, the rarity of CTC clusters and the limitations of capture techniques have blocked research progress. In vitro CTC clusters model can help us further understand the biological properties of CTC clusters and their clinical significance. It is worth noting that the biological variability of in vitro CTC clusters model due to different culture conditions has a non-negligible impact on the experimental results. Therefore, it is necessary to examine the biological similarity of in vitro CTC cluster models with clinical CTC clusters. Here, we optimized the culture method for the in vitro CTC cluster model based on the physiological environment of CTC in the circulatory system, and more importantly, we emphasized the importance of evaluating the in vitro CTC cluster models with reference to the biological characteristics of reported real CTC clusters, and assessed the similarity of the in vitro CTC clusters model, providing a reliable method for the study of CTC clusters.