Patient-derived scaffolds uncover breast cancer promoting properties of the microenvironment

Landberg, Göran; Fitzpatrick, Paul; Isakson, Pauline; Jonasson, Emma; Karlsson, Jan Ch; Larsson, Erik; Svanström, Andreas; Rafnsdóttir, Svanheiður; Persson, Emma; Gustafsson, Anna; Andersson, Daniel; Rosendahl, Jennifer; Petronis, Šarūnas; Ranji, Parmida; Gregersson, Pernilla; Magnusson, Yvonne; Håkansson, Joakim; Ståhlberg, Anders

doi:10.1016/j.biomaterials.2019.119705

Cited by 48 publications

(81 citation statements)

References 72 publications

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“…23,33,34 We have previously reported that PDS derived from breast cancer tissue promote CSC activity in different breast cancer cell lines. 8 We have now shown that the colorectal PDS model enhances the expression of some stemness and pluripotency genes, which further supports the physiological relevance of our PDS model in in vitro studies. The reduced proliferation and the CSC enrichment observed in the PDS model can be largely attributed to the passage from 2D to 3D culturing conditions.…”

Section: Colorectal Pds Can Be Repopulated With Breast Cancer Cell supporting

confidence: 78%

“…Although colorectal CSC are commonly studied in spheroid models, 31 these are cell line dependent 32 and do not account for the complexity of the TME, which has been frequently identified as an important promoting factor in CSC enrichment 23,33,34 . We have previously reported that PDS derived from breast cancer tissue promote CSC activity in different breast cancer cell lines 8 . We have now shown that the colorectal PDS model enhances the expression of some stemness and pluripotency genes, which further supports the physiological relevance of our PDS model in in vitro studies.…”

Section: Discussionmentioning

confidence: 99%

“…The results indicated that the PDS system can be employed on colorectal tumors as easily as breast cancer tissue, which we have previously reported. 8 By using mild detergent washes to decellularize colorectal samples, recellularization with standardized cancer cell lines was easily achieved and even non-colorectal cell lines repopulated colorectal PDS, which demonstrated the robust nature of the PDS technique. Similar to other 3D cell culture systems, cancer cell lines grown on colorectal PDS increased the RNA expression of pluripotency markers, while proliferation markers were generally downregulated.…”

Section: Introductionmentioning

confidence: 98%

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Patient‐derived scaffolds as a model of colorectal cancer

et al. 2020

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Section: Colorectal Pds Can Be Repopulated With Breast Cancer Cell supporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Patient‐derived scaffolds as a model of colorectal cancer

et al. 2020

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“…Recently, we showed that patient-derived scaffolds (PDSs) produced from decellularized breast cancer tissue retained the natural ECM architecture and composition, representing the complexity of the tumor microenvironment (Landberg et al, 2020). Breast cancer cells that repopulated PDSs were influenced by the microenvironment and were clearly mimicking the in vivo-like cell-ECM interaction.…”

Section: Introductionmentioning

confidence: 99%

Breast cancer patient‐derived scaffolds as a tool to monitor chemotherapy responses in human tumor microenvironments

Leiva

Garré

Gustafsson

et al. 2020

Journal Cellular Physiology

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Breast cancer is a heterogeneous disease where the tumor microenvironment, including extracellular components, plays a crucial role in tumor progression, potentially modulating treatment response. Different approaches have been used to develop three-dimensional models able to recapitulate the complexity of the extracellular matrix. Here, we use cell-free patient-derived scaffolds (PDSs) generated from breast cancer samples that were recellularized with cancer cell lines as an in vivo-like culture system for drug testing. We show that PDS cultured MCF7 cancer cells increased their resistance against the front-line chemotherapy drugs 5-fluorouracil, doxorubicin and paclitaxel in comparison to traditional two-dimensional cell cultures. The gene expression of the environmentally adapted cancer cells was modulated in different ways depending on the drug and the concentration used. High doses of doxorubicin reduced cancer stem cell features, whereas 5-fluorouracil increased stemness and decreased the proliferative phenotype. By using PDSs repopulated with other breast cancer cell lines, T-47D and MDA-MB-231, we observed both general and cell line specific drug responses. In summary, PDSs can be used to examine the extracellular matrix influence on cancer drug responses and for testing novel compounds in in vivo-like microenvironments.

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“…To address these issues, 3D cell culture models are a reliable alternative, providing experimentally accessible human models to study the biological processes of cancer. Several 3D culture platforms such as spheroids, organoids, hydrogels, 3D scaffolds, 3D bio-printing, and microfluidics have attempted the recreation of certain aspects of tumor microenvironments present in tissues including the brain [30][31][32][33][34][35][36], breast [37][38][39][40][41][42][43], ovarian [44][45][46][47][48][49][50][51], bone [52][53][54][55][56][57][58], liver [59][60][61][62][63][64][65], lung [66][67][68][69][70][71][72], colon [73][74][75][76]…”

Section: Mimicking Tme In Three-dimensionsmentioning

confidence: 99%

Mimicking tumor hypoxia and tumor-immune interactions employing three-dimensional in vitro models

Bhattacharya

Calar

Puente

2020

J Exp Clin Cancer Res

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The heterogeneous tumor microenvironment (TME) is highly complex and not entirely understood. These complex configurations lead to the generation of oxygen-deprived conditions within the tumor niche, which modulate several intrinsic TME elements to promote immunosuppressive outcomes. Decoding these communications is necessary for designing effective therapeutic strategies that can effectively reduce tumor-associated chemotherapy resistance by employing the inherent potential of the immune system. While classic two-dimensional in vitro research models reveal critical hypoxia-driven biochemical cues, threedimensional (3D) cell culture models more accurately replicate the TME-immune manifestations. In this study, we review various 3D cell culture models currently being utilized to foster an oxygen-deprived TME, those that assess the dynamics associated with TME-immune cell penetrability within the tumor-like spatial structure, and discuss state of the art 3D systems that attempt recreating hypoxia-driven TME-immune outcomes. We also highlight the importance of integrating various hallmarks, which collectively might influence the functionality of these 3D models. This review strives to supplement perspectives to the quickly-evolving discipline that endeavors to mimic tumor hypoxia and tumor-immune interactions using 3D in vitro models.

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Patient-derived scaffolds uncover breast cancer promoting properties of the microenvironment

Cited by 48 publications

References 72 publications

Patient‐derived scaffolds as a model of colorectal cancer

Patient‐derived scaffolds as a model of colorectal cancer

Breast cancer patient‐derived scaffolds as a tool to monitor chemotherapy responses in human tumor microenvironments

Mimicking tumor hypoxia and tumor-immune interactions employing three-dimensional in vitro models

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