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Review
. 2022;1(4):678-681.
doi: 10.1016/j.gastha.2022.04.019.

A Novel Pancreatic Cancer Mini-tumor Model to Study Desmoplasia and Myofibroblastic Cancer-Associated Fibroblast Differentiation

T J Harryvan  1 , L J A C Hawinkels  1 ; mini-tumor workgroup; A Östman  2 , P Ten Dijke  3 , C Strell  4 , M Hornsveld  1   3
Collaborators, Affiliations
Review

A Novel Pancreatic Cancer Mini-tumor Model to Study Desmoplasia and Myofibroblastic Cancer-Associated Fibroblast Differentiation

T J Harryvan et al. Gastro Hep Adv. 2022.
No abstract available

Keywords: CAF, cancer-associated fibroblasts; MT, minitumor; MyCAF, myofibroblastic CAF; PDAC, pancreatic ductal adenocarcinoma; PDGFR, platelet-derived growth factor receptor; PDO, pancreatic tumor-derived organoids; TGFβ, transforming growth factor β; αSMA, α-smooth muscle actin.

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Figures

Figure 1
Figure 1
PDGF-BB and TGFβ drive pancreatic cancer MT formation including desmoplasia and MyCAF differentiation. (A) Examples of 3 different PDAC primary tumors (A, B, C) stained for PDGFRβ (green) PDGFRα (magenta), αSMA (red), pSMAD2 (white), and pan-cytokeratin (cyan). Scalebar 100 μm. Arrows indicate PDGFRα+ cells. (B) Relative mRNA expression of HMGA2, E-cadherin N-Cadherin, Vimentin (VIM), αSMA, LGR5 and OLFM4 in PDO1 monocultures, PDO1 + hPS1 homogenous and direct contact MT cocultures grown in organoid growth (OG) medium ± TGFβ inhibitor (TGFβi) or PDGF-BB for 10 days (n = 3). (C) Schematic overview of suspension MT generation. (D) Representative bright-field images (top panel) of PDO1 + hPS1 MTs cultured in OG, OG + PDGF-BB, OG-TGFβ inhibitor, and OG + PDGF-BB-TGFβ inhibitor (MT) medium for 10 days. These were subsequently processed and stained for PDGFRβ (green) PDGFRα (magenta), αSMA (red), pSMAD2 (white), and pan-cytokeratin (cyan) (bottom panel). n = 3; Scalebar 100 μm.
Figure 2
Figure 2
Characteristics and applicability of the MT model. (A) FFPE PDO2 + hPS1 and PDO3 + hPS1 MTs cultured in OG or MT (OG + PDGF-BB-TGFβ inhibitor) medium for 10 days stained for PDGFRβ (green), PDGFRα (magenta), αSMA (red), pSMAD2 (white), and pan-cytokeratin (cyan). Scalebar 100 μm. (B) Representative FFPE PDO1 + primary CAF1 (pCAF), pCAF2, and pCAF3 MTs cultured in OG or MT medium for 10 days stained for PDGFRβ (green), PDGFRα (magenta), αSMA (red), pSMAD2 (white), and pan-cytokeratin (cyan); n = 2. (C) FFPE FNADO + FNA-CAF MTs cultured in OG or MT medium for 10 days compared to FNADO + FNA-CAF xenograft, stained for PDGFRβ (green), PDGFRα (magenta), αSMA (red), pSMAD2 (white), and pan-cytokeratin (cyan); n = 3, scalebar 100 μm. (D) Monoculture organoids (PDO4) and MTs consisting of PDO4 and hPS1 fibroblasts were treated with oxaliplatin (100 μm) and imaged for 7 days using phase-contrast microscopy. On day 7, viability was assessed using calcein AM staining, and cells were subsequently processed for hematoxylin & eosin (H&E) staining. Scalebar 250 μm.
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References

    1. Siegel R.L., et al. CA Cancer J Clin. 2022;72:7–33. - PubMed
    1. Tuveson D., et al. Science. 2019;364:952–955. - PubMed
    1. Lau H.C.H., et al. Nat Rev Gastroenterol Hepatol. 2020;17:203–222. - PubMed
    1. Kobayashi H., et al. Nat Rev Gastroenterol Hepatol. 2019;16:282–295. - PubMed
    1. Helms E., et al. Cancer Discov. 2020;10:648–656. - PMC - PubMed

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