Proteolytic remodeling of 3D bioprinted tumor microenvironments

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Rasti Boroojeni, FatemehLinköpings universitet,Biofysik och bioteknik,Tekniska fakulteten (author)

Proteolytic remodeling of 3D bioprinted tumor microenvironments

Article/chapterEnglish2024

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IOP Publishing Ltd,2024
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LIBRIS-ID:oai:DiVA.org:liu-200482
https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-200482URI
https://doi.org/10.1088/1758-5090/ad17d1DOI

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Language:English
Summary in:English

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Funding Agencies|Knut and Alice Wallenberg Foundation (KAW) [2016.0231, 2021.0186]; European Research Council [101044665]; Carl Tryggers Stiftelse
In native tissue, remodeling of the pericellular space is essential for cellular activities and is mediated by tightly regulated proteases. Protease activity is dysregulated in many diseases, including many forms of cancer. Increased proteolytic activity is directly linked to tumor invasion into stroma, metastasis, and angiogenesis as well as all other hallmarks of cancer. Here we show a strategy for 3D bioprinting of breast cancer models using well-defined protease degradable hydrogels that can facilitate exploration of the multifaceted roles of proteolytic extracellular matrix remodeling in tumor progression. We designed a set of bicyclo[6.1.0]nonyne functionalized hyaluronan (HA)-based bioinks cross-linked by azide-modified poly(ethylene glycol) (PEG) or matrix metalloproteinase (MMP) degradable azide-functionalized peptides. Bioprinted structures combining PEG and peptide-based hydrogels were proteolytically degraded with spatial selectivity, leaving non-degradable features intact. Bioprinting of tumor-mimicking microenvironments using bioinks comprising human breast cancer cells (MCF-7) and fibroblast in hydrogels with different susceptibilities to proteolytic degradation shows that MCF-7 proliferation and spheroid size were significantly increased in protease degradable hydrogel compartments, but only in the presence of fibroblasts. In the absence of fibroblasts in the stromal compartment, cancer cell proliferation was reduced and did not differ between degradable and nondegradable hydrogels. The interactions between spatially separated fibroblasts and MCF-7 cells consequently resulted in protease-mediated remodeling of the bioprinted structures and a significant increase in cancer cell spheroid size, highlighting the close interplay between cancer cells and stromal cells in the tumor microenvironment and the influence of proteases in tumor progression.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
bioprinting; hydrogel; breast cancer; cancer model; protease degradability

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Naeimipour, SajjadLinköpings universitet,Biofysik och bioteknik,Tekniska fakulteten(Swepub:liu)sajna98 (author)
Lifwergren, PhilipLinköpings universitet,Biofysik och bioteknik,Tekniska fakulteten(Swepub:liu)phili65 (author)
Abrahamsson, AnnelieLinköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US(Swepub:liu)annab29 (author)
Dabrosin, CharlottaLinköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US(Swepub:liu)chada67 (author)
Selegård, RobertLinköpings universitet,Biofysik och bioteknik,Tekniska fakulteten(Swepub:liu)robse34 (author)
Aili, DanielLinköpings universitet,Biofysik och bioteknik,Tekniska fakulteten(Swepub:liu)danai11 (author)
Linköpings universitetBiofysik och bioteknik (creator_code:org_t)

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In:Biofabrication: IOP Publishing Ltd16:21758-50821758-5090

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