Ovarian cancer (OvCa) is a leading cause of mortality from gynecologic
malignancy due to its disseminated peritoneal
metastasis. The tumor microenvironment dominates epithelial-mesenchymal transition (EMT) development and impacts
cancer metastasis as well as mediates drug resistance. Tumour cell interaction with the
collagen I matrix is critical in OvCa development. To better understand the role of the
collagen matrix and the underlying mechanisms in the early stage of OvCa invasion, we developed a three-dimensional (3D) culture model in vitro by embedding OvCa cells within
collagen I to recreate the architecture of a solid tumour. Our results showed that tumour spheroids formed in the 3D
collagen model displayed good viability and decreased growth rates, which partly recapitulated the growth behavior of in vivo tumour cells.
Collagen I enhanced the OvCa cell motility/invasion capability by up-regulating the expression of
MMPs and α5β1
integrin. Moreover, highly invasive OvCa cells in
collagen showed the overexpression of mesenchymal markers (
N-cadherin,
vimentin and
fibronectin) and transcriptional factors (Snail and Slug). EMT-associated TGF-β1/Smad4 and Wnt5b/β-
catenin signaling pathways were significantly up-regulated accordingly. Additionally, a remarkably enhanced drug resistance to chemotherapeutics was also detected in the 3D cultures. Collectively, the bioengineered 3D
collagen models could recapitulate the in vivo tumour-like microenvironment and reflect some biological characteristics of human OvCa more accurately. The
collagen I matrix promoted local invasion via EMT and enhanced the multidrug resistance in OvCa. This system might serve as a comprehensive in vitro model to better understand the manifold mechanisms of OvCa
metastasis and also provide a robust tool for screening new anti-
ovarian cancer therapeutics.