RT Journal Article
SR Electronic
T1 Molecular and functional heterogeneity of cancer associated fibroblasts in high-grade serous ovarian cancer
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 519728
DO 10.1101/519728
A1 Ali Hussain
A1 Veronique Voisin
A1 Stephanie Poon
A1 Julia Dmytryshyn
A1 Cory Richman
A1 Jalna Meens
A1 Victor W Ho
A1 Kwan Ho Tang
A1 Joshua Paterson
A1 Blaise Clarke
A1 Marcus Q Bernardini
A1 Gary D Bader
A1 Benjamin G Neel
A1 Laurie E Ailles
YR 2019
UL http://biorxiv.org/content/early/2019/02/07/519728.abstract
AB Recent studies indicate that cancer-associated fibroblasts (CAFs) are phenotypically and functionally heterogeneous. However, little is known about CAF subtypes and the roles they play in cancer progression. Here we identify and characterize two CAF subtypes that coexist within high grade serous ovarian cancers: Fibroblast activation protein (FAP)-high (FH) CAFs resemble the classical myofibroblast-type CAF, whereas FAP-low (FL) CAFs possesses a preadipocyte-like molecular signature. Patients with predominantly FH CAFs have significantly worse outcomes than patients with predominantly FL CAFs. FH CAFs contract collagen gels and aggressively promote proliferation, invasion and therapy resistance of cancer cells, whereas FL CAFs do not. Overexpression of the FL-specific transcription factor TCF21 in FH CAFs decreases their ability to promote gel contraction, invasion, and in vivo tumor growth. Understanding CAF subtypes in more detail could lead to better patient stratification and novel therapeutic strategies.