Molecular insights of metastasis and cancer progression derived using 3D cancer spheroid co-culture in vitro platform

Modi, Unnati; Makwana, Pooja; Vasita, Rajesh

doi:10.1016/j.critrevonc.2021.103511

Cited by 14 publications

(10 citation statements)

References 171 publications

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“…VEGF-induced tumor EMT and invasion via AKT and Wnt singling pathway, where the phosphorylation of paladin and vimentin and the expression of β-catenin were enhanced. In addition, endothelin-1, a peptide produced by endothelial cells, activated integrin-linked kinase (ILK) signaling pathways, leading to increased intracellular β-catenin concentration, decreased E-cad expression, and enhanced EMT [46]. The elevated N-cad expression of coculture compared to monoculture in figure 6(C) was the final summation results of the signaling pathway affected by the endothelial cells.…”

Section: Constructed Migrating Stage Liver Tumor Model Under Tgf-β Tr...mentioning

confidence: 98%

Spheroid on-demand printing and drug screening of endothelialized hepatocellular carcinoma model at different stages

Liu

Zhou

et al. 2023

Biofabrication

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Hepatocellular carcinoma (HCC) poses a significant threat to human health and medical care. Its dynamic microenvironment and stages of development will influence the treatment strategies in clinics. Reconstructing tumor-microvascular interactions in different stages of the microenvironment is an urgent need for in vitro tumor pathology research and drug screening. However, the absence of tumor aggregates with paracancerous microvascular and staged tumor-endothelium interactions leads to bias in the antitumor drug responses. Herein, a spheroid-on-demand manipulation strategy was developed to construct staged endothelialized HCC models for drug screening. Pre-assembled HepG2 spheroids were directly printed by alternating viscous and inertial force jetting with high cell viability and integrity. A semi-open microfluidic chip was also designed to form a microvascular connections with high density, narrow diameter, and curved morphologies. According to the single or multiple lesions in stages Ⅰ or Ⅱ HCC, endothelialized HCC models from micrometer to millimeter scale with dense tumor cell aggregation and paracancerous endothelial distribution were successively constructed. A migrating stage Ⅲ HCC model was further constructed under TGF-β treatment, where the spheroids exhibited a more mesenchymal phenotype with a loose cell connection and spheroid dispersion. Finally, the stage Ⅱ HCC model showed stronger drug resistance compared to the stage Ⅰ model, while the stage III showed a more rapid response. The corresponding work provides a widely applicable method for the reproduction of tumor-microvascular interactions at different stages and holds great promise for the study of tumor migration, tumor-stromal cell interactions, and the development of anti-tumor therapeutic strategies.

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Section: Constructed Migrating Stage Liver Tumor Model Under Tgf-β Tr...mentioning

confidence: 98%

Spheroid on-demand printing and drug screening of endothelialized hepatocellular carcinoma model at different stages

Liu

Zhou

et al. 2023

Biofabrication

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“…Therefore, research on cellular invasion plays a crucial role in enhancing antimetastasis treatments. [60,61] Herein, self-sustaining hydrogels were applied as a supporting matrix for 3D in vitro osteosarcoma. 143B cells were selected due to their highly aggressive and metastatic characteristics.…”

Section: D Model For Osteosarcomamentioning

confidence: 99%

A Self‐Sustaining Hydrogels with Autonomous Supply of Nutrients and Bioactive Domains for 3D Cell Culture

Zargarzadeh,

Gomes,

Patrício

et al. 2023

Adv Funct Materials

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Photo‐crosslinkable platelet lysate (PL)‐based hydrogels have been proven to support human‐derived cell cultures owing to their high content of bioactive molecules, such as cytokines and growth factors. As a unique self‐maintained and biocompatible 3D scaffold, the recently reported self‐feeding hydrogels with enzyme‐empowered degradation capacity have shown high biological performance in vitro and in vivo. To take advantage of all features of both PL and self‐feeding hydrogels, here UV responsive laminaran‐methacrylate (LamMA) and PL‐methacrylate (PLMA) derivatives plus glucoamylase (GA), which significantly improve the overall features of a 3D system, is coupled. This self‐sustaining hybrid hydrogel emerges as a unique scaffold due to the sustained delivery of glucose produced via enzymatic degradation of laminaran while granting the release of growth factors through the presence of PL. This biomaterial is applied to fabricate high‐throughput freestanding microgels with controlled geometric shapes. Furthermore, this multicomponent hybrid hydrogel is successfully implemented as the first reported glucose supplier bioink to manufacture intricate and precisely defined cell‐laden structures using a support matrix. Finally, such hydrogels are utilized as a proof of concept to serve as 3D in vitro cancer models, with the aim of recapitulating the tumor microenvironment.

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“…[ 2,3 ] The 3D cell culture system provides cancer spheroids imitating the spatiotemporal organization and physiological properties like metabolism, gene expression, cellular signaling, and topography alike to the cancer cell of the tumor. [ 4–6 ] As an in vitro lung adenocarcinoma or non‐small cell lung cancer model, A549, a cell line has been frequently preferred by researchers. For developing in vitro A549 3D spheroid commonly used techniques are ultra‐low attachment [ 7 ] surface, [ 8,9 ] hanging drop assays, [ 10 ] 3D microprinted scaffold, [ 11 ] microfluidics, and hydrogel‐based scaffolds have been widely used.…”

Section: Introductionmentioning

confidence: 99%

Differential Migration and Proliferation Potential of the Hydrogel Aided 3D Tumoroid

Modi

Kedaria

Vasita

2022

Macromolecular Bioscience

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For substantial in vitro cancer biology research, the 3D cell culture method has now been regarded as more suitable model expected to be recapitulating maximum in vivo tumor mass relevance. Despite of available techniques to develop in vitro 3D models, a system availing a physiologically relevant in vitro 3D model of primary lung adenocarcinoma with extracellular matrix (ECM) mimicry and similar tumorigenic properties still remains a quest. Thus, in the present study, chemically modified Dextran-Chitosan (MDC) hydrogel has been developed as a 3D tumoroid aiding scaffold. The 3D A549 tumoroids aided by the MDC scaffold have physiologically relevant proliferation, migration, invasive potential, and Gefitinib [targeting epidermal growth factor receptor (EGFR)] efficacy as compared to the 2D cultured cells. The surface topography and wettability of hydrogel availed in vivo micro tumor mass mimicking Lung adenocarcinoma 3D in vitro model. Thus, opening an innovative avenue for elucidating the disease mechanism and drug efficacy on relevant 3D cancer models in vitro.

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Molecular insights of metastasis and cancer progression derived using 3D cancer spheroid co-culture in vitro platform

Cited by 14 publications

References 171 publications

Spheroid on-demand printing and drug screening of endothelialized hepatocellular carcinoma model at different stages

Spheroid on-demand printing and drug screening of endothelialized hepatocellular carcinoma model at different stages

A Self‐Sustaining Hydrogels with Autonomous Supply of Nutrients and Bioactive Domains for 3D Cell Culture

Differential Migration and Proliferation Potential of the Hydrogel Aided 3D Tumoroid

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