Remodeling of the extracellular matrix in human ovarian cancer can be reflected in increased collagen concentration, changes in alignment within fibrils and fibers and/or up-regulation of different collagen isoforms. We used pixel-based SHG polarization microscopy analyses to probe these molecular changes in in vitro gel models and ex vivo human ovarian tissues (normal stroma, benign tumors, and high grade serous tumors) by: i) determination of i) the alpha helical pitch angle via the single axis molecular model, ii) dipole alignment within fibrils via anisotropy, and iii) chirality via SHG circular dichroism (SHG-CD).  The methods were first verified using a series of self- assembled gel models comprised of known fractions of Col I and Col III, where the latter has been implicated in both benign ovarian tumors as well as high grade serous tumors.  The three polarization-based metrics all successfully differentiated the resulting collagen isoform content. These metrics were similarly applied to ex vivo human tissues. The largest differences were between normal stroma and benign tumors, consistent with gene expression showing Col III is up-regulated in the latter. The different tissues also displayed statistically differing SHG anisotropies and SHG-CD responses, consistent with either Col III incorporation or randomization of Col I alignment within benign and high-grade tumors fibrils. These results collectively indicate the fibril assemblies are distinct in all tissues and likely result from synthesis of new collagen rather than remodeling of existing collagen. Importantly, this analysis is label-free and interrogates sub-resolution collagen structure on intact tissues, without the need for conventional structural biology tools. We suggest these polarization-based metrics could form the basis of a new classification scheme and complement conventional classification based on genetic profiles and conventional histology.<br/>

Analysis of collagen architecture alterations in human ovarian cancer via SHG polarization resolved microscopy

256th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.