4DB Center: Physics of Metastasis over Time and Space

Early cancer screening in a simple non-invasive way is one of the important challenges of modern medical science. At early stages, the progression of carcinogenesis is often accompanied by the nanoscale morphological changes in the internal structure of a cell.  Detecting such subtle nanoscale changes for cytological diagnosis of cancer has been stymied due to the diffraction-limited resolution of existing optical imaging techniques (such as microscopy).  To address this need, we developed partial wave spectroscopic (PWS) microscopy that provides unprecedented insights into the nanoscale architecture of either living or fixed biological cells. Our results from nanostructure models indicated that PWS microscopy is sensitive to structures that are less than ~ 40nm.  This was further confirmed from our studies on cell lines and animal models which showed that PWS microscopy is capable of differentiating cells of different genetic knockdowns that are otherwise similar under conventional microscopy. 

Using PWS microscopy, we observed changes to cell nanoarchitecture not only in tumor cells but also in the microscopically normal-appearing cells present outside of the tumor. Although genetic and epigenetic alterations have been previously observed in the field of carcinogenesis, these cells were considered morphologically normal.  Our data show organ-wide alterations in cell nanoarchitecture. This appears to be a general event in carcinogenesis, which is supported by our data in three types of cancer: colon, pancreatic and lung cancers where the nanoarchitecture changes were observed in cells from rectum, duodenal mucosa and buccal mucosa respectively. These results have important implications in that PWS microscopy can be used as a new methodology to identify patients harboring malignant or a premalignant tumors  by interrogating easily accessible tissue sites distant from the location of the lesion.