Biophysical changes caused by altered MUC13 expression in pancreatic cancer cells. (March 2020)

• Record Type: Journal Article
• Authors: Massey, Andrew E.; Doxtater, Kyle A.; Yallapu, Murali M.; Chauhan, Subhash C.
• Is Part Of: Micron. Volume 130(2020)
• Publication Date: 2020-03
• Subjects: MUC13 -- Pancreatic cancer -- Nanoindentation; Microscopy -- Periodicals; Electron Probe Microanalysis -- Periodicals; Microscopy -- Periodicals; Microscopie -- Périodiques; Microscopy; Periodicals; 502.82
• DOI: 10.1016/j.micron.2019.102822
• Languages: English
• ISSNs: 0968-4328

Abstract

Graphical abstract: Highlights: Pancreatic cancer is known to aberrantly express mucin protein MUC13. High levels of MUC13 are associated with enhanced aggressiveness in multiple cancers. Nanomechanical analysis of MUC13 modulated cells shows unique biophysical changes. Observed physical changes agree with literature consensus on reduced modulus in more aggressive or invasive cells. Abstract: Background: Pancreatic cancer is one of the most lethal cancers in the United States. This is partly due to the difficulty in early detection of this disease as well as poor therapeutic responses to currently available regimens. Our previous reports suggest that mucin 13 (MUC13, a transmembrane mucin common to gastrointestinal cells) is aberrantly expressed in this disease state, and has been implicated with a worsened prognosis and an enhanced metastatic potential in PanCa. However, virtually no information currently exists to describe the biophysical ramifications of this protein. Methods: To demonstrate the biophysical effect of MUC13 in PanCa, we generated overexpressing and knockdown model cell lines for PanCa and subsequently subjected them to various biophysical experiments using atomic force microscopy (AFM) and cellular aggregation studies. Results: AFM-based nanoindentation data showed significant biophysical effects with MUC13 modulation in PanCa cells. The overexpression of MUC13 in Panc-1 cells led to an expected decrease in modulus, and a corresponding decrease in adhesion. With MUC13 knockdown, HPAF-II cells exhibited an increased modulus and adhesion. These results were confirmed with altered cell-cell adhesion as seen with aggregation assays. Conclusions: MUC13 led to significant biophysical changes in PanCa cells and which exhibited characteristic phenotypic changes in cells demonstrated in previous work from our lab. This work gives insight into the use of biophysical measurements that could be used to help diagnose or monitor cancers as well as determine the effects of genetic alterations at a mechanical level.