Modulating Three-Dimensional Microenvironment with Hyaluronan of Different Molecular Weights Alters Breast Cancer Cell Invasion Behavior

• DOI: 10.1021/acsami.6b15187
• Publication Date: 2017-02-27T15:44:08Z
• Authors: Yu-fang Zhao; Shu-pei Qiao; Shu-liang Shi; Li-fen Yao; Xiao-lu Hou; Chun-feng Li; Feng-Huei Lin; Kai Guo; Alaka Acharya; Xiong-biao Chen; Yongzhan Nie; Wei-ming Tian
• Keywords: SKBR3; Hyaluronidase

Hyaluronan (HA), a polymer with various molecular weights (MW) found in tumor microenvironments, is associated malignant progression of breast cancer. Reducing the amount high-MW HA microenvironment by hyaluronidase promising approach for cancer treatment. However, whether generation fragments negatively affects cells remains to be determined. Furthermore, forms three-dimensional (3D) networks cross-linking other extracellular molecules function. Therefore, model mimicking cross-linked network required determine effect on cells. To clarify differential roles low (HA35) versus high (HA117) MW cell phenotype, 3D culture system was set up covalently alginate and investigating behavior 4T-1 SKBR3 alongside two-dimensional (2D) control. The results show invasion migration abilities are significantly enhanced presence HA35 but inhibited HA117 both 2D monolayers spheroids. effects epithelial-mesenchymal transition (EMT) phenotype were further confirmed terms regulation E-cadherin vimentin as important EMT markers at cellular mRNA levels. Additional experiments CD44-Twist signaling pathway might involved HA117. These have implications respect understanding role development design therapeutic approaches based eradication hyaluronidase.