Human pancreatic stellate cells modulate 3D collagen alignment to promote the migration of pancreatic ductal adenocarcinoma cells.
A hallmark of pancreatic ductal adenocarcinoma (PDAC) is the ability for cancer cells to aggressively infiltrate and navigate through a dense stroma during the metastatic process. Key features of the PDAC stroma include an abundant population of activated pancreatic stellate cells (PSCs) and highly aligned collagen fibers; however, important questions remain regarding how collagen becomes aligned and what the biological manifestations are. To better understand how PSCs, aligned collagen, and PDAC cells might cooperate during the transition to invasion, we utilized a microchannel-based in vitro tumor model and advanced imaging technologies to recreate and examine in vivo-like heterotypic interactions. We found that PSCs participate in a collaborative process with cancer cells by orchestrating the alignment of collagen fibers that, in turn, are permissive to enhanced cell migration. Additionally, direct contact between PSCs, collagen, and PDAC cells is critical to invasion and co-migration of both cell types. This suggests PSCs may accompany and assist in navigating PDAC cells through the stromal terrain. Together, our data provides a new role for PSCs in stimulating the metastatic process and underscores the importance of collagen alignment in cancer progression.
Department of Biomedical Engineering, University of Wisconsin, Madison, WI, USA.|Laboratory for Optical and Computational Instrumentation (LOCI), University of Wisconsin, Madison, WI, USA.|Morgridge Institute for Research, Madison, WI, USA.
Cole R
CR
Drifka
Department of Surgical Pathology, University of Wisconsin, Madison, WI, USA.|University of Wisconsin Comprehensive Carbone Cancer Center, Madison, WI, USA.
Agnes G
AG
Loeffler
Laboratory for Optical and Computational Instrumentation (LOCI), University of Wisconsin, Madison, WI, USA.
Corinne R
CR
Esquibel
University of Wisconsin Comprehensive Carbone Cancer Center, Madison, WI, USA.|Department of Surgery, University of Wisconsin, Madison, WI, USA.
Sharon M
SM
Weber
Department of Biomedical Engineering, University of Wisconsin, Madison, WI, USA.|Laboratory for Optical and Computational Instrumentation (LOCI), University of Wisconsin, Madison, WI, USA.|Morgridge Institute for Research, Madison, WI, USA.|University of Wisconsin Comprehensive Carbone Cancer Center, Madison, WI, USA.
Kevin W
KW
Eliceiri
Department of Biomedical Engineering, University of Wisconsin, Madison, WI, USA. wjkao@hku.hk.|University of Wisconsin Comprehensive Carbone Cancer Center, Madison, WI, USA. wjkao@hku.hk.|Department of Surgery, University of Wisconsin, Madison, WI, USA. wjkao@hku.hk.|Faculties of Medicine and Engineering, University of Hong Kong, Pokfulam Road, Pokfulam, Hong Kong. wjkao@hku.hk.
W John
WJ
Kao
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D001696:Biomechanical Phenomena; D002465:Cell Movement; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D056656:Lab-On-A-Chip Devices; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D058954:Pancreatic Stellate Cells / Q000473:pathology*; D010447:Peptide Hydrolases / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
D003094:Collagen; D054460:rho-Associated Kinases; D010447:Peptide Hydrolases
3D co-culture; Collagen; Invasion; Pancreatic cancer; Tumor microenvironment