Phenotypic, genomic, and transcriptomic heterogeneity in a pancreatic cancer cell line

Abstract

Genomic heterogeneity in pancreatic cancer has been widely studied in recent years because of the development of next generation of genome-wide sequencing technology. However, little is known whether this genomic heterogeneity will drive phenotypic heterogeneity and the underlying mechanism that links genomic variations to phenotypic heterogeneity in pancreatic cancer. To study these questions, by using single-cell flow sorting, we established four clones from MiaPaCa-2, a cell line derived from human pancreatic primary tumors. Indeed, these four MiaPaCa-2 clones show heterogenous phenotypes including distinct cellular morphology and differential proliferation and migration rate. Further genomic DNA sequencing analysis of MiaPaCa-2 clones demonstrates genomic heterogeneity, suggesting heterogeneity of the population or genomic instability. Lastly, our mRNA-sequencing analysis of the four MiaPaCa-2 clones identified that ITGAV is necessary and sufficient for morphology change of MiaPaCa-2 subclones, suggesting that ITGAV might be a major regulator in controlling the heterogeneity in MiaPaCa-2 cell line. In conclusion, our study demonstrated the heterogeneity of pancreatic cancer cells at genomic, transcriptomic, and phenotypic levels.