Cellular Fate Decision by Autocrine and Paracrine in Tumor

Although cellular communication via secretion has been recognized as a critical step in determining cellular fates, its inherent complexity inhibits our in-depth understanding. If either input to cellular system or measurement of secretions is clarified, our intuitive understanding can be further improved. Herein, we demonstrate a microfluidic single-cell analysis platform that can clarify microenvironments around single cells through a predefined fluidics. The microfluidic single-cell analysis platform is capable of isolating thousands of single cells to individual culture chambers and culturing them in a biochemically defined environment during more than 5-time divisions. The automatic microscope imaging allows tracing the lineage of individual cells and discovering the effect of autocrine and paracrine. The experiment using non-small lung cancer cell line, H1975, shows that the cellular proliferation is linearly dependent to the exposure extent to autocrine secretion, the senescent cells supports neighbor cells' proliferation by paracrine secretion, and the combinatory effect of autocrine and paracrine can cause the local variation of proliferation to be more than 5 times. This study can provide biological clues how cancer cells, in a short time (i.e., < a day), determine their fates by secretomic response rather than genomic mutation, extracellular matrix and mechanical factors and how cancer metastasis can be successful in vivo.