Novel prognostic markers within the CD44‐stromal ligand network in pancreatic cancer

Abstract The dense stroma in pancreatic cancer tumours is rich in secreted extracellular matrix proteins and proteoglycans. Secreted hyaluronan, osteopontin and type IV collagen sustain oncogenic signalling by interactions with CD44s and its variant isoform CD44v6 on cancer cell membranes. Although...

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Main Authors: Oskar Franklin (Author), Ola Billing (Author), Daniel Öhlund (Author), Anette Berglund (Author), Carl Herdenberg (Author), Wanzhong Wang (Author), Urban Hellman (Author), Malin Sund (Author)
Format: Book
Published: Wiley, 2019-04-01T00:00:00Z.
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001 doaj_daafc6812e4b40a48a53a6037d01fc30
042 |a dc 
100 1 0 |a Oskar Franklin  |e author 
700 1 0 |a Ola Billing  |e author 
700 1 0 |a Daniel Öhlund  |e author 
700 1 0 |a Anette Berglund  |e author 
700 1 0 |a Carl Herdenberg  |e author 
700 1 0 |a Wanzhong Wang  |e author 
700 1 0 |a Urban Hellman  |e author 
700 1 0 |a Malin Sund  |e author 
245 0 0 |a Novel prognostic markers within the CD44‐stromal ligand network in pancreatic cancer 
260 |b Wiley,   |c 2019-04-01T00:00:00Z. 
500 |a 2056-4538 
500 |a 10.1002/cjp2.122 
520 |a Abstract The dense stroma in pancreatic cancer tumours is rich in secreted extracellular matrix proteins and proteoglycans. Secreted hyaluronan, osteopontin and type IV collagen sustain oncogenic signalling by interactions with CD44s and its variant isoform CD44v6 on cancer cell membranes. Although well established in animal and in vitro models, this oncogenic CD44‐stromal ligand network is less explored in human cancer. Here, we use a pancreatic cancer tissue microarray from 69 primary tumours and 37 metastatic lymph nodes and demonstrate that high tumour cell expression of CD44s and, surprisingly, low stromal deposition of osteopontin correlate with poor survival independent of established prognostic factors for pancreatic cancer. High stromal expression of hyaluronan was a universal trait of both primary tumours and metastatic lymph nodes. However, hyaluronan species of different molecular mass are known to function differently in pancreatic cancer biology and immunohistochemistry cannot distinguish between them. Using gas‐phase electrophoretic molecular mobility analysis, we uncover a shift towards high molecular mass hyaluronan in pancreatic cancer tissue compared to normal pancreas and at a transcriptional level, we find that hyaluronan synthesising HAS2 correlates positively with CD44. The resulting prediction that high molecular mass hyaluronan would then correlate with poor survival in pancreatic cancer was confirmed in serum samples, where we demonstrate that hyaluronan >27 kDa measured before surgery is an independent predictor of postoperative survival. Our findings confirm the prognostic value of CD44 tissue expression and highlight osteopontin tissue expression and serum high molecular mass hyaluronan as novel prognostic markers in pancreatic cancer. 
546 |a EN 
690 |a pancreatic cancer 
690 |a CD44 
690 |a hyaluronan 
690 |a type IV collagen 
690 |a osteopontin 
690 |a biomarkers 
690 |a Pathology 
690 |a RB1-214 
655 7 |a article  |2 local 
786 0 |n The Journal of Pathology: Clinical Research, Vol 5, Iss 2, Pp 130-141 (2019) 
787 0 |n https://doi.org/10.1002/cjp2.122 
787 0 |n https://doaj.org/toc/2056-4538 
856 4 1 |u https://doaj.org/article/daafc6812e4b40a48a53a6037d01fc30  |z Connect to this object online.