| First Author | Begum HM | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 11187 |
| PubMed ID | 31371796 | Mgi Jnum | J:285948 |
| Mgi Id | MGI:6387384 | Doi | 10.1038/s41598-019-47593-8 |
| Citation | Begum HM, et al. (2019) Spatial Regulation of Mitochondrial Heterogeneity by Stromal Confinement in Micropatterned Tumor Models. Sci Rep 9(1):11187 |
| abstractText | Heterogeneity of mitochondrial activities in cancer cells exists across different disease stages and even in the same patient, with increased mitochondrial activities associated with invasive cancer phenotypes and circulating tumor cells. Here, we use a micropatterned tumor-stromal assay (muTSA) comprised of MCF-7 breast cancer cells and bone marrow stromal cells (BMSCs) as a model to investigate the role of stromal constraints in altering the mitochondrial activities of cancer cells within the tumor microenvironment (TME). Using microdissection and RNA sequencing, we revealed a differentially regulated pattern of gene expression related to mitochondrial activities and metastatic potential at the tumor-stromal interface. Gene expression was confirmed by immunostaining of mitochondrial mass, and live microscopic imaging of mitochondrial membrane potential (DeltaPsim) and optical redox ratio. We demonstrated that physical constraints by the stromal cells play a major role in DeltaPsim heterogeneity, which was positively associated with nuclear translocation of the YAP/TAZ transcriptional co-activators. Importantly, inhibiting actin polymerization and Rho-associated protein kinase disrupted the differential DeltaPsim pattern. In addition, we showed a positive correlation between DeltaPsim level and metastatic burden in vivo in mice injected with MDA-MB-231 breast cancer cells. This study supports a new regulatory role for the TME in mitochondrial heterogeneity and metastatic potential. |
