S100 family proteins are linked to organoid morphology and EMT in pancreatic cancer

Ronnie Ren Jie Low; Ka Yee Fung; Hugh Gao; Adele Preaudet; Laura F Dagley; Jumana Yousef; Belinda Lee; Samantha J Emery-Corbin; Paul M Nguyen; Rune H Larsen; Nadia J Kershaw; Antony W Burgess; Peter Gibbs; Frédéric Hollande; Michael D W Griffin; Sean M Grimmond; Tracy L Putoczki

doi:10.1038/s41418-023-01126-z

S100 family proteins are linked to organoid morphology and EMT in pancreatic cancer

Cell Death Differ. 2023 May;30(5):1155-1165. doi: 10.1038/s41418-023-01126-z. Epub 2023 Feb 24.

Authors

Ronnie Ren Jie Low^{1

2

3}, Ka Yee Fung^{1

2}, Hugh Gao^{3

4

5

6}, Adele Preaudet^{1

2}, Laura F Dagley^{1

2}, Jumana Yousef^{1

2}, Belinda Lee^{1

2}, Samantha J Emery-Corbin^{1

2}, Paul M Nguyen^{3

4}, Rune H Larsen^{1

2}, Nadia J Kershaw^{1

2}, Antony W Burgess^{1

2}, Peter Gibbs^{1

2}, Frédéric Hollande^{3

4}, Michael D W Griffin⁷, Sean M Grimmond^{3

4}, Tracy L Putoczki^{8

9}

Affiliations

¹ The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.
² Department of Medical Biology, The University of Melbourne, Parkville, VIC, 3052, Australia.
³ University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, 3000, Australia.
⁴ Department of Clinical Pathology, University of Melbourne, Parkville, VIC, 3000, Australia.
⁵ Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, VIC, 3168, Australia.
⁶ Department of Molecular and Translational Science, Monash University, Clayton, VIC, 3800, Australia.
⁷ Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC, 3000, Australia.
⁸ The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia. putoczki.t@wehi.edu.au.
⁹ Department of Medical Biology, The University of Melbourne, Parkville, VIC, 3052, Australia. putoczki.t@wehi.edu.au.

Abstract

Epithelial-mesenchymal transition (EMT) is a continuum that includes epithelial, partial EMT, and mesenchymal states, each of which is associated with cancer progression, invasive capabilities, and ultimately, metastasis. We used a lineage-traced sporadic model of pancreatic cancer to generate a murine organoid biobank from primary and secondary tumors, including sublines that underwent partial EMT and complete EMT. Using an unbiased proteomics approach, we found that organoid morphology predicts the EMT state, and the solid organoids are associated with a partial EMT signature. We also observed that exogenous TGFβ1 induces solid organoid morphology that is associated with changes in the S100 family, complete EMT, and the formation of high-grade tumors. S100A4 may be a useful biomarker for predicting EMT state, disease progression, and outcome in patients with pancreatic cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line, Tumor
Epithelial-Mesenchymal Transition
Humans
Mice
Pancreatic Neoplasms* / pathology
S100 Proteins* / genetics
S100 Proteins* / metabolism

Substances

S100 Proteins