Fibulin-2 Is a Driver of Malignant Progression in Lung Adenocarcinoma

• DOI: 10.1371/journal.pone.0067054
• Publication Date: 2013-06-10T21:14:29Z
• Authors: Brandi N. Baird; Mark J. Schliekelman; Young-Ho Ahn; Yulong Chen; Jonathon D. Roybal; Bartley J. Gill; Dhruva K. Mishra; Baruch Erez; Michael O’Reilly; Yanan Yang; Mayuri Patel; Xin Liu; Nishan Thilaganathan; Irina V. Larina; Mary E. Dickinson; Jennifer L. West; Don L. Gibbons; Diane D. Liu; Min P. Kim; John M. Hicks; Ignacio I. Wistuba; Samir M. Hanash; Jonathan M. Kurie
• Keywords: Fibulin; Tumor progression

The extracellular matrix of epithelial tumors undergoes structural remodeling during periods uncontrolled growth, creating regional heterogeneity and torsional stress. How integrity is maintained in the face dynamic biophysical forces largely undefined. Here we investigated role fibulin-2, a glycoprotein that functions biomechanically as an inter-molecular clasp thereby facilitates supra-molecular assembly. Fibulin-2 was abundant human lung adenocarcinomas highly expressed tumor cell lines derived from mice develop metastatic adenocarcinoma co-expression mutant K-ras p53. Loss-of-function experiments cells revealed fibulin-2 required for to grow metastasize syngeneic mice, surprising finding given other intra-tumoral types are known secrete fibulin-2. However, grew metastasized equally well Fbln2-null -wild-type littermates, implying malignant progression dependent specifically upon cell-derived which could not be offset by cellular sources deficiency impaired ability migrate invade Boyden chambers, create stiff cross-link secreted collagen, adhere collagen. We conclude driver plays unexpected collagen cross-linking adherence