Ovarian Cancer Cell Adhesion/Migration Dynamics on Micro-Structured Laminin Gradients Fabricated by Multiphoton Excited Photochemistry

Bioengineering

Ruei-Yu He³  Visar Ajeti³  Shean-Jen Chen²  Molly A. Brewer¹  Paul J. Campagnola³ 

[1] Department of Obstetrics and Gynecology, University of Connecticut Health Center, Farmington, CT 06030, USA; E-Mail:;Department of Engineering Science, National Cheng Kung University, Tainan 701, Taiwan; E-Mail:;Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53717, USA; E-Mails:

关键词: ovarian cancer;    ECM;    haptotaxis;    contact guidance;    morphology;    cytoskeleton;   

DOI  :  10.3390/bioengineering2030139

来源: mdpi

【 摘 要 】

Haptotaxis, i.e., cell migration in response to adhesive gradients, has been previously implicated in cancer metastasis. A better understanding of cell migration dynamics and their regulation could ultimately lead to new drug targets, especially for cancers with poor prognoses, such as ovarian cancer. Haptotaxis has not been well-studied due to the lack of biomimetic, biocompatible models, where, for example, microcontact printing and microfluidics approaches are primarily limited to 2D surfaces and cannot produce the 3D submicron features to which cells respond. Here we used multiphoton excited (MPE) phototochemistry to fabricate nano/microstructured gradients of laminin (LN) as 2.5D models of the ovarian basal lamina to study the haptotaxis dynamics of a series of ovarian cancer cells. Using these models, we found that increased LN concentration increased migration speed and also alignment of the overall cell morphology and their cytoskeleton along the linear axis of the gradients. Both these metrics were enhanced on LN compared to BSA gradients of the same design, demonstrating the importance of both topographic and ECM cues on the adhesion/migration dynamics. Using two different gradient designs, we addressed the question of the roles of local concentration and slope and found that the specific haptotactic response depends on the cell phenotype and not simply the gradient design. Moreover, small changes in concentration strongly affected the migration properties. This work is a necessary step in studying haptotaxis in more complete 3D models of the tumor microenvironment for ovarian and other cancers.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.