In Vivo Clotting Breast Cancer Stem Cells and Platelets: A New Endogenous Precursor of Metastasis Progression.

摘要

Most cancer-related deaths arise from metastasis produced by circulating tumor cells (CTCs). A new concept of this research is that circulating cancer stem cell (CSC)-platelet aggregates (CSCPA) represent the most aggressive subset of CTCs responsible for breast cancer metastasis. The goal of this proposal is to identify and count CSCPAs in vivo in preclinical models of metastatic breast cancer, and to define the correlation of CSCPA amount with metastasis development. We developed a novel, in vivo multicolor photoacoustic (PA) flow cytometry (PAFC) platform for the detection of CSCPAs using the principle of flow cytometry, negative and positive PA contrasts, multispectral high-pulse-repetition-rate lasers, bioconjugated nanoparticles and a mouse model of human breast cancer. Using this approach, we provided a proof-of-concept for highly sensitive detection of CSCPAs and individual CSCs in real biological environments in a whole body in vivo. For the first time, we demonstrated the ability of CSCs to form aggregates with platelets (CSCPAs) in blood circulation of tumorbearing mice. Furthermore we showed that the number of CSCPAs increased during development of metastatic disease. Obtained preclinical results can advance general understanding of cancer stem cell biology and metastasis progression as well as will be used as the basis for initiating highly innovative clinical research in cancer patients.