Poster #086, University of California, San Francisco
Investigating the Role of Collagen-Mediated Matrix Stiffness in Pancreatic Tumor Progression and Metastasis Using ColR/R Mouse Models
Mentors: Ghmkin Hassan, PhD; Valerie Weaver, PhD
Pancreatic cancer has a high mortality rate largely driven by early metastasis and late detection. A collagen-rich extracellular matrix stiffens the tumor microenvironment, promoting immune evasion. In this project, we investigated whether collagen accumulation and tissue stiffness promote pancreatic tumor progression and metastasis by comparing genetically modified, collagenase-resistant ColR/R mice to wild-type (WT) mice. We hypothesize that ColR/R mice will develop more aggressive tumors and greater metastasis than WT mice. WT and ColR/R mice were genotyped by polymerase chain reaction (PCR), pancreatic tumors were established in both groups. After two months, pancreatic and lung tissues were collected, embedded in paraffin, and sectioned onto microscope slides. Tissue sections were stained with Hematoxylin and Eosin (H&E), Picrosirius Red, and a collagen probe (CNA35-GFP), and subsequently imaged. Digital image analysis quantified collagen content and metastatic lesions. In the absence of tumors, ColR/R mice had significantly more collagen and stiffer pancreatic tissue than WT mice. Tumor-bearing ColR/R mice showed higher collagen content and greater lung metastasis compared to the tumor-bearing WT mice. These results suggest that the microenvironment stiffness, driven by collagen content, promotes tumor aggressiveness and metastasis, highlighting matrix stiffness as a potential therapeutic target.