Dive into Single, Seek Out Multiple: Probing Cancer Metastases via Single-Cell Sequencing and Imaging Techniques

SIMPLE SUMMARY: Treating cancer metastasis is the biggest challenge in clinical practice. It is largely due to our limited understanding of the complex process, which involves not only the evolution and/or selection of heterogeneous primary tumor cells to metastatic tumors, but also interaction and/or adaption with various types of cells in different microenvironments, including temporally in the circulation system. These limitations are currently resolved by single-cell technologies. This review summarizes recent applications of single-cell technologies in metastatic studies, highlights the unique findings, and discusses the future directions. ABSTRACT: Metastasis is the cause of most cancer deaths and continues to be the biggest challenge in clinical practice and laboratory investigation. The challenge is largely due to the intrinsic heterogeneity of primary and metastatic tumor populations and the complex interactions among cancer cells and cells in the tumor microenvironment. Therefore, it is important to determine the genotype and phenotype of individual cells so that the metastasis-driving events can be precisely identified, understood, and targeted in future therapies. Single-cell sequencing techniques have allowed the direct comparison of the genomic and transcriptomic changes among different stages of metastatic samples. Single-cell imaging approaches have enabled the live visualization of the heterogeneous behaviors of malignant and non-malignant cells in the tumor microenvironment. By applying these technologies, we are achieving a spatiotemporal precision understanding of cancer metastases and clinical therapeutic translations.