Decellularized human colorectal cancer matrices polarize macrophages towards an anti-inflammatory phenotype promoting cancer cell invasion via CCL18

Pinto, Marta; Rios, Elisabete; Silva, A.C.; Neves, Sara C.; Caires, Hugo R.; Pinto, Ana Nóbrega; Durães, Cecília; Carvalho, Filomena A.; Cardoso, Ana Patrícia; Santos, Nuno C.; Barrias, Cristina C.; Nascimento, Diana S.; Pinto-do-Ó, Perpétua; Barbosa, Mário A.; Carneiro, Fátima; Oliveira, Maria José

doi:10.1016/j.biomaterials.2017.02.004

Cited by 112 publications

(103 citation statements)

References 51 publications

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“…As reported by others, GAG loss is an inevitable side effect of DET, because glycans are one of the most easily leachable component of the ECM and are also present in large amount on cell membranes that are totally removed along the DET process. Notably, in our study the loss of GAG is smaller compared with other similar studies (Pinto et al, ); moreover, the method we used for their quantification is not sensible to Hyaluronan, a glycan that is known to be excessive accumulated in breast (Auvinen et al, ), gastric (Setala et al, ), and colorectal (Kobel et al, ) cancer tissues, probably underestimating the total concentration, especially in tumor samples, that in our hands seems more realistic with the histological readout.…”

Section: Discussioncontrasting

confidence: 48%

“…GAG preservation is crucial to maintain the biological activity of our patient‐derived scaffolds. In fact, it has been demonstrated that GAG bind many growth factors and allow the specific and organized localization of ligands and associated proteins, such as mucins, complement, metalloproteases and their inhibitors, latent TGF‐β, divers growth factors, and chemokines (Pinto et al, ). As reported by others, GAG loss is an inevitable side effect of DET, because glycans are one of the most easily leachable component of the ECM and are also present in large amount on cell membranes that are totally removed along the DET process.…”

Section: Discussionmentioning

confidence: 99%

“…This technical advance made possible to develop 3D tumor cell culture models in which ECM and tissue architecture were maintained, providing a potentially useful approach for producing more significant cancer models (Ghajar & Bissell, ). The advantage of using biological‐derived matrices instead of synthetic polymers for 3D tumor engineering in vitro is that part of main structural proteins and soluble factors are present already in the decellularized scaffold, enabling a more reliable tissue reconstruction (Pinto et al, ). Up to now, 3D scaffolds have been developed as platforms for in vitro studies of cancer cell growth, proliferation, migration (Ridky, Chow, Wong, & Khavari, ) and to approach a new way for the discovery of cancer‐initiating and cancer‐related genes (Chen et al, ).…”

Section: Introductionmentioning

confidence: 99%

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Decellularized colorectal cancer matrix as bioactive microenvironment for in vitro 3D cancer research

Piccoli

D’Angelo

Crotti

et al. 2018

Journal Cellular Physiology

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Three-dimensional (3D) cancer models are overlooking the scientific landscape with the primary goal of bridging the gaps between two-dimensional (2D) cell lines, animal models and clinical research. Here, we describe an innovative tissue engineering approach applied to colorectal cancer (CRC) starting from decellularized human biopsies in order to generate an organotypic 3D-bioactive model. This in vitro 3D system recapitulates the ultrastructural environment of native tissue as demonstrated by histology, immunohistochemistry, immunofluorescence and scanning electron microscopy analyses. Mass spectrometry of proteome and secretome confirmed a different stromal composition between decellularized healthy mucosa and CRC in terms of structural and secreted proteins. Importantly, we proved that our 3D acellular matrices retained their biological properties: using CAM assay, we observed a decreased angiogenic potential in decellularized CRC compared with healthy tissue, caused by direct effect of DEFA3. We demonstrated that following a 5 days of recellularization with HT-29 cell line, the 3D tumor matrices induced an over-expression of IL-8, a DEFA3-mediated pathway and a mandatory chemokine in cancer growth and proliferation. Given the biological activity maintained by the scaffolds after decellularization, we believe this approach is a powerful tool for future pre-clinical research and screenings.

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Section: Discussioncontrasting

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Decellularized colorectal cancer matrix as bioactive microenvironment for in vitro 3D cancer research

Piccoli

D’Angelo

Crotti

et al. 2018

Journal Cellular Physiology

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“…Another study investigated the impact of human colorectal tumor ECM on macrophage polarization, and showed that tumor ECM-educated macrophages develop into M2 macrophages in the tumor microenvironment [29]. In this study, paired tissue derived from CRC patients were decellularized to the native ECM, where native tissue characteristics (architecture and mechanical properties) and major ECM components (fibronectin, laminin, collagens type I and IV, and hyaluronic acid) are preserved.…”

Section: Effect Of Tams-induced Ecm Remodeling On Crc Growthmentioning

confidence: 99%

The Role of Tumor-Associated Macrophages in Colorectal Carcinoma Progression

Zhong¹,

Chen²,

Yang³

2018

Cell Physiol Biochem

109

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Tumor-associated macrophages (TAMs) are one of the most abundant immune cells in the tumor microenvironment, and they play a pivotal role in prompting the various tumor growth. However, the role of TAMs in colorectal carcinoma (CRC) is controversial, because a few papers report that TAMs is beneficial to CRC patients. In this review, we discuss the good or bad roles of TAMs in CRC progression. Interestingly, recent studies provide strong evidence that TAMs facilitate CRC growth, but do not exert tumor suppressive activities. TAMs can stimulate CRC growth by altering extracellular matrix remodeling, tumor metabolism, angiogenesis, as well as the tumor microenvironment. Therefore, TAMs could serve as a target for CRC therapeutic treatment.

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“…[5][6][7] Concerning macrophages, the results are also contradictory since M1 and M2 macrophages are associated with tumour growth inhibition and stimulation, respectively. 5,8 However, CD68+ macrophages have been linked to a favourable outcome. 4,6 Neutrophils, mast cells and dendritic cells have been also implicated in CRC prognosis to a lesser extent.…”

Section: Amp Studentmentioning

confidence: 99%

New Insights Into the Role of Tissue Eosinophils in the Progression of Colorectal Cancer: A Literature Review

Saraiva

Carneiro²

2018

Acta Med Port

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RESUMOIntrodução: O papel dos eosinófilos na carcinogénese colorretal tem sido discutido em várias publicações científicas. O objetivo deste estudo foi o de rever o valor dos eosinófilos tecidulares no prognóstico do cancro colorretal, enfatizando a sua identificação, mensuração e associação com as características clinicopatológicas da doença. Material e Métodos:Utilizámos os motores de busca PubMed e Web of Science para pesquisar estudos que associassem os eosinófilos tecidulares com o prognóstico do cancro colorretal.Resultados: Selecionámos 15 estudos para a nossa revisão. Maioritariamente, a análise do infiltrado foi realizada através da coloração de hematoxilina-eosina, com criação de scores. A maioria dos trabalhos descreveu a eosinofilia tecidular como um fator de prognóstico favorável no cancro colorretal e estabeleceu uma associação inversa entre ela e o comportamento metastático dos tumores. A associação com outros fatores de prognóstico foi por vezes abordada, com resultados inconsistentes. A eosinofilia tecidular diminuiu na progressão adenoma-carcinoma. Discussão:Vários mecanismos têm sido propostos para explicar a quimiotaxia de eosinófilos para os tecidos tumorais e a sua interação com as células neoplásicas, sugerindo o envolvimento dos eosinófilos na progressão do cancro colorretal. Apesar de não existir um sistema de avaliação validado, a eosinofilia tecidular associada a tumores pode constituir um parâmetro histopatológico de prognóstico no cancro colorretal. Conclusão:As evidências disponíveis associam a presença de eosinófilos no microambiente do cancro colorretal com a modulação da sua progressão. O impacto clínico deste achado deve ser estudado no futuro. Palavras-chave: Material and Methods:We used PubMed and Web of Science search engines to retrieve studies that looked at the association between tissue eosinophils and colorectal cancer prognosis. Results:We selected 15 studies for our review. In the majority of the studies, eosinophils were identified in hematoxylin-eosin stained sections and scores were generated for analysis. Most of the studies pointed to tumour-associated tissue eosinophilia as a favourable prognostic marker in colorectal cancer and found an inverse association between eosinophil count and the metastatic potential of these neoplasms. The association between tumour-associated tissue eosinophilia and established prognostic markers of colorectal cancer was assessed in some studies, with inconsistent results. Additionally, tumour-associated tissue eosinophilia decreased with the adenoma-carcinoma progression of colorectal lesions.Discussion: Several mechanisms have been proposed regarding eosinophil chemoatraction to tumour tissues and eosinophil-cancer cell cross-talk, suggesting that eosinophils are actively involved in colorectal cancer progression. Although a scoring system is still lacking, tumour-associated tissue eosinophilia meets the criteria of a convenient histopathological prognosticator in colorectal cancer. Conclusion:Collectively, current evidence associa...

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Decellularized human colorectal cancer matrices polarize macrophages towards an anti-inflammatory phenotype promoting cancer cell invasion via CCL18

Cited by 112 publications

References 51 publications

Decellularized colorectal cancer matrix as bioactive microenvironment for in vitro 3D cancer research

Decellularized colorectal cancer matrix as bioactive microenvironment for in vitro 3D cancer research

The Role of Tumor-Associated Macrophages in Colorectal Carcinoma Progression

New Insights Into the Role of Tissue Eosinophils in the Progression of Colorectal Cancer: A Literature Review

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