Matrix stiffness mediates pancreatic cancer chemoresistance through induction of exosome hypersecretion in a cancer associated fibroblasts-tumor organoid biomimetic model

Xiao, Weikun; Pahlavanneshan, Mahsa; Eun, Chae-Young; Zhang, Xinyu; DeKalb, Charlene; Mahgoub, Bayan; Knaneh-Monem, Hanaa; Shah, Syed Niaz Ali; Sohrabi, Alireza; Seidlits, Stephanie K.; Hill, Reuben

doi:10.1016/j.mbplus.2022.100111

Cited by 31 publications

(21 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To increase the cellular heterogeneity and complete these models, co-culture systems and multicellular organoid have started to be established with, e.g., fibroblasts, cancer-associated fibroblasts, adipocytes, and vessels. However, these models are extremely unstable and their long-term treatments face several difficulties [19,23,50,54]. There are some data about the treatment sensitivity differences of these models, which highlight that 3D structures and cellular complexity could influence the experimental results of in vitro therapeutic drug sensitivity tests [51,55].…”

Section: Discussionmentioning

confidence: 99%

Characterisation of 3D Bioprinted Human Breast Cancer Model for In Vitro Drug and Metabolic Targeting

Dankó

Petővári

Raffay

et al. 2022

IJMS

View full text Add to dashboard Cite

Monolayer cultures, the less standard three-dimensional (3D) culturing systems, and xenografts are the main tools used in current basic and drug development studies of cancer research. The aim of biofabrication is to design and construct a more representative in vivo 3D environment, replacing two-dimensional (2D) cell cultures. Here, we aim to provide a complex comparative analysis of 2D and 3D spheroid culturing, and 3D bioprinted and xenografted breast cancer models. We established a protocol to produce alginate-based hydrogel bioink for 3D bioprinting and the long-term culturing of tumour cells in vitro. Cell proliferation and tumourigenicity were assessed with various tests. Additionally, the results of rapamycin, doxycycline and doxorubicin monotreatments and combinations were also compared. The sensitivity and protein expression profile of 3D bioprinted tissue-mimetic scaffolds showed the highest similarity to the less drug-sensitive xenograft models. Several metabolic protein expressions were examined, and the in situ tissue heterogeneity representing the characteristics of human breast cancers was also verified in 3D bioprinted and cultured tissue-mimetic structures. Our results provide additional steps in the direction of representing in vivo 3D situations in in vitro studies. Future use of these models could help to reduce the number of animal experiments and increase the success rate of clinical phase trials.

show abstract

Section: Discussionmentioning

confidence: 99%

Characterisation of 3D Bioprinted Human Breast Cancer Model for In Vitro Drug and Metabolic Targeting

Dankó

Petővári

Raffay

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…The physics of cancer is an emerging field of oncology which highlights the mechanical properties of the tumor microenvironment (TME), focusing on the role of cell-ECM interactions in cancer disease and metastasis ( Burgos-Panadero, Lucantoni, et al, 2019 ; Grant et al, 2022 ; Kpeglo et al, 2022 ; Liu et al, 2022 ; Xiao et al, 2022 ). As glycoproteins interact with integrins and are involved in cell adhesion and migration pathways, molecules similar to VN, such as FN have been used in cancer mechanotransduction studies ( Missirlis and Spatz, 2014 ; Elosegui-Artola et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Vitronectin-based hydrogels recapitulate neuroblastoma growth conditions

Monferrer

Dobre

Trujillo

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The tumor microenvironment plays an important role in cancer development and the use of 3D in vitro systems that decouple different elements of this microenvironment is critical for the study of cancer progression. In neuroblastoma (NB), vitronectin (VN), an extracellular matrix protein, has been linked to poor prognosis and appears as a promising therapeutic target. Here, we developed hydrogels that incorporate VN into 3D polyethylene glycol (PEG) hydrogel networks to recapitulate the native NB microenvironment. The stiffness of the VN/PEG hydrogels was modulated to be comparable to the in vivo values reported for NB tissue samples. We used SK-N-BE (2) NB cells to demonstrate that PEGylated VN promotes cell adhesion as the native protein does. Furthermore, the PEGylation of VN allows its crosslinking into the hydrogel network, providing VN retention within the hydrogels that support viable cells in 3D. Confocal imaging and ELISA assays indicate that cells secrete VN also in the hydrogels and continue to reorganize their 3D environment. Overall, the 3D VN-based PEG hydrogels recapitulate the complexity of the native tumor extracellular matrix, showing that VN-cell interaction plays a key role in NB aggressiveness, and that VN could potentially be targeted in preclinical drug studies performed on the presented hydrogels.

show abstract

“…Weikun et al built a bio-mimetic 3D co-culture model to integrate the complex tumor organoids and used sEV release inhibitor climbazole and imipramine to treat the PDAC organoids, finding that climbazole and imipramine inhibited the growth of organoids and chemoresistance by preventing the release of CAF tumor organoid-derived sEVs. [141] In another study, Mikamori et al found GEM resistance in PDAC cells might be relevant to miR-155, which controlled genes required for sEV synthesis. [142] The authors used RAB27B siRNA (siRAB27B) to transfect PDAC cells and downregulated RAB27B effectively.…”

Section: Inhibition Of Cancer-derived Sev Formation and Secretionmentioning

confidence: 99%

“…Climbazole and imipramine prevented the release of PDAC-derived sEVs and inhibited the growth of organoids and chemoresistance [141] PDAC-derived sEVs (Panc-1, MiaPaCa-2, PSN-1)…”

Section: Climbazole Imipraminementioning

confidence: 99%

Cancer-derived small extracellular vesicles: emerging biomarkers and therapies for pancreatic ductal adenocarcinoma diagnosis/prognosis and treatment

Zhang

Campbell²,

Walsh³

et al. 2022

J Nanobiotechnol

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal cancers worldwide with high mortality, which is mainly due to the lack of reliable biomarkers for PDAC diagnosis/prognosis in the early stages and effective therapeutic strategies for the treatment. Cancer-derived small extracellular vesicles (sEVs), which carry various messages and signal biomolecules (e.g. RNAs, DNAs, proteins, lipids, and glycans) to constitute the key features (e.g. genetic and phenotypic status) of cancer cells, are regarded as highly competitive non-invasive biomarkers for PDAC diagnosis/prognosis. Additionally, new insights on the biogenesis and molecular functions of cancer-derived sEVs pave the way for novel therapeutic strategies based on cancer-derived sEVs for PDAC treatment such as inhibition of the formation or secretion of cancer-derived sEVs, using cancer-derived sEVs as drug carriers and for immunotherapy. This review provides a comprehensive overview of the most recent scientific and clinical research on the discovery and involvement of key molecules in cancer-derived sEVs for PDAC diagnosis/prognosis and strategies using cancer-derived sEVs for PDAC treatment. The current limitations and emerging trends toward clinical application of cancer-derived sEVs in PDAC diagnosis/prognosis and treatment have also been discussed.

show abstract

Matrix stiffness mediates pancreatic cancer chemoresistance through induction of exosome hypersecretion in a cancer associated fibroblasts-tumor organoid biomimetic model

Cited by 31 publications

References 48 publications

Characterisation of 3D Bioprinted Human Breast Cancer Model for In Vitro Drug and Metabolic Targeting

Characterisation of 3D Bioprinted Human Breast Cancer Model for In Vitro Drug and Metabolic Targeting

Vitronectin-based hydrogels recapitulate neuroblastoma growth conditions

Cancer-derived small extracellular vesicles: emerging biomarkers and therapies for pancreatic ductal adenocarcinoma diagnosis/prognosis and treatment

Contact Info

Product

Resources

About