A profound remodeling of the collagen in the extracellular matrix (ECM) occurs in human ovarian cancer but it unknown how this affects tumor growth, where this understanding could lead to better diagnostics and therapeutic approaches. Here, we investigate the role of these specific alterations in collagen morphology on cell function by using multiphoton excited (MPE) polymerization to fabricate 3D biomimetic models of the ovarian stroma based on Second Harmonic Generation images. This process is akin to 3D printing except is performed at much higher resolution (~0.5 microns) and with the proteins that comprise the native ECM. We use this technique to create collagen scaffolds with complex, 3D submicron morphology representing the morphology in normal stroma, high risk stroma, benign tumors, and high grade cancer ovarian tissues. The models are seeded with different cancer cell lines and this allows decoupling of the roles of cell characteristics (metastatic potential) and ECM structure and composition (normal vs cancer) on migration dynamics. We found the malignant stromal structure promoted enhanced motility, and also cell and cytoskeletal alignment with respect to fibers. Conversely, normal and cancer cells on the normal stroma had the weakest response to the matrix morphology. While collagen alignment is known to affect cell dynamics, we further found small changes in the collagen fiber morphology (e.g. periodicity) had large effects on the resulting migration dynamics. These models cannot be synthesized by other conventional fabrication methods and we suggest the MPE image-based fabrication method will enable a variety of studies in cancer biology.

Date Published: 13 March 2019
PDF
Proc. SPIE 10883, Three-Dimensional and Multidimensional Microscopy: Image Acquisition and Processing XXVI, 108830Y (13 March 2019); doi: 10.1117/12.2510094

Published in SPIE Proceedings Vol. 10883:
Three-Dimensional and Multidimensional Microscopy: Image Acquisition and Processing XXVI
Thomas G. Brown; Tony Wilson, Editor(s)