Abstract
Circulating tumor cell (CTC) clusters may represent one of the key mechanisms initiating the metastasis process. However, the series of pathophysiologic events by which CTC clusters originate, enter the circulation, and reach the distant sites remain to be identified. The cellular and molecular mechanisms that provide survival advantage for CTC clusters during the transit in the blood stream are also still largely unknown. Understanding the biology of CTC clusters is critical to assess this unified scheme employed by cancer and to device strategies to overcome key pathways responsible for their improved metastatic potential. CTC clusters remain an underdeveloped area of research begging the attention of multidisciplinary cancer research teams. Here, we provide insight on existing preclinical evidence on the potential mechanisms leading to CTC cluster formation and dissemination and on processes that may offer survival advantage. We also offer our perspective on future directions to delineate the role of CTC clusters in metastatic cascade and discuss their clinical significance. Cancer Res; 78(4); 845-52. ©2018 AACR.
Highlights
Solid tumors can release a surprisingly high number of circulating tumor cells (CTC) everyday into the circulation [1]
CTCs originating from primary tumors are considered transitional in the search for a new home, most of these cells are fated to die in circulation owing to mechanical and environmental trauma such as shear forces, oxidative stress, and attack by the immune system
CTC clusters originating from a primary tumor could "self-seed" the original site or travel to distant sites of metastasis
Summary
Solid tumors can release a surprisingly high number of circulating tumor cells (CTC) everyday into the circulation [1]. CTC clusters originating from a primary tumor could "self-seed" the original site or travel to distant sites of metastasis. CTC clusters arising from a (micro)metastatic site could return to the primary tumor site or the original (micro)metastatic site or could travel to another distant site of metastasis. To support this hypothesis, tumor self-seeding has been a well-accepted concept for CTCs in general [7]. The study evaluated self-seeding concept only for the primary tumors, cross-seeding of primary and (micro)metastatic tumors can be envisioned
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