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Influence of extracellular matrix composition on tumour cell behaviour in a biomimetic in vitro model for hepatocellular carcinoma
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- Calitz, Carlemi (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi,Uppsala Univ, Dept Med Cell Biol, Husargatan 3,Box 571, S-75431 Uppsala, Sweden.
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- Rosenquist, Jenny (författare)
- Uppsala universitet,Makromolekylär kemi,Uppsala Univ, Dept Chem, Angstrom Lab, Polymer Chem, Box 538, S-75121 Uppsala, Sweden.
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- Degerstedt, Oliver (författare)
- Uppsala universitet,Institutionen för farmaci,Institutionen för farmaceutisk biovetenskap,Uppsala Univ, Dept Pharmaceut Biosci, Uppsala, Sweden.
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- (creator_code:org_t)
- 2023-01-13
- 2023
- Engelska.
- Ingår i: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 13:1
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- The tumor micro-environment (TME) of hepatocellular carcinoma (HCC) consists out of cirrhotic liver tissue and is characterized by an extensive deposition of extracellular matrix proteins (ECM). The evolution from a reversible fibrotic state to end-stage of liver disease, namely cirrhosis, is characterized by an increased deposition of ECM, as well as changes in the exact ECM composition, which both contribute to an increased liver stiffness and can alter tumor phenotype. The goal of this study was to assess how changes in matrix composition and stiffness influence tumor behavior. HCC-cell lines were grown in a biomimetic hydrogel model resembling the stiffness and composition of a fibrotic or cirrhotic liver. When HCC-cells were grown in a matrix resembling a cirrhotic liver, they increased proliferation and protein content, compared to those grown in a fibrotic environment. Tumour nodules spontaneously formed outside the gels, which appeared earlier in cirrhotic conditions and were significantly larger compared to those found outside fibrotic gels. These tumor nodules had an increased expression of markers related to epithelial-to-mesenchymal transition (EMT), when comparing cirrhotic to fibrotic gels. HCC-cells grown in cirrhotic gels were also more resistant to doxorubicin compared with those grown in fibrotic gels or in 2D. Therefore, altering ECM composition affects tumor behavior, for instance by increasing pro-metastatic potential, inducing EMT and reducing response to chemotherapy.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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- Calitz, Carlemi
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- Khaled, Jaafar
- Kopsida, Maria
- Fryknäs, Mårten
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- Lennernäs, Hans
- Samanta, Ayan
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