The Chicken Egg Chorioallantoic Membrane (CAM) Model as an In Vivo Method for the Investigation of the Invasion and Metastasis Cascade of Malignant Tumor Cells

2021 ◽  
pp. 17-26
Author(s):  
Jörg H. Leupold ◽  
Nitin Patil ◽  
Heike Allgayer
Keyword(s):  
Tumor Cells ◽  
Malignant Tumor ◽  
Chorioallantoic Membrane ◽  
Invasion And Metastasis ◽  
Chicken Egg ◽  
Cam Model

The chick embryo chorioallantoic membrane model: a research approach for ex vivo and in vivo experiments

2021 ◽  
Vol 28 ◽  
Author(s):  
Ana Isabel Fraguas-Sánchez ◽  
Cristina Martín-Sabroso ◽  
Ana Isabel Torres-Suárez
Keyword(s):  
Animal Models ◽  
Chorioallantoic Membrane ◽  
New Drugs ◽  
Biological Research ◽  
Research Areas ◽  
Chick Chorioallantoic Membrane ◽  
Biodistribution Studies ◽  
Toxicological Studies ◽  
Cam Model

Background: The chick chorioallantoic membrane (CAM) model has attracted a great deal of interest in pharmaceutical and biological research as an alternative or complementary in vivo assay to animal models. Traditionally, CAM assay has been widely used to perform some toxicological studies, specifically to evaluate the skin, ocular and embryo toxicity of new drugs and formulations, and perform angiogenesis studies. Due to the possibility to generate the tumors onto the CAM, this model has also become an excellent strategy to evaluate the metastatic potential of different tumours and test the efficacy of novel anticancer therapies in vivo. Moreover, in the recent years, its use has considerably grown in other research areas, including the evaluation of new anti-infective agents, the development of biodistribution studies and tissue engineering research. Objectives: This manuscript provides a critical overview of the use of CAM model in pharmaceutical and biological research, especially to test the toxicity of new drugs and formulations and the biodistribution and the efficacy of novel anticancer and anti-infective therapies, analyzing its advantages and disadvantages compared to animal models. Conclusion: The chick chorioallantoic membrane model shows great utility in several research areas, such as cancer, toxicology, biodistribution studies and anti-infective therapies. In fact, it has become an intermediate stage between in vitro experiments and animal studies, and, in the case of toxicological studies (skin and ocular toxicity), has even replaced the animal models.

scholarly journals In vivo invasion of modified chorioallantoic membrane by tumor cells: the role of cell surface-bound urokinase.

1988 ◽  
Vol 107 (6) ◽  
pp. 2437-2445 ◽  
Author(s):  
L Ossowski
Keyword(s):  
Cell Surface ◽  
Plasminogen Activator ◽  
Tumor Cells ◽  
Chorioallantoic Membrane ◽  
Human Tumor ◽  
Chick Embryo Chorioallantoic Membrane ◽  
Catalytically Active ◽  
Surface Receptor

The ability of the chick embryo chorioallantoic membrane (CAM) to withstand invasion by tumor cells can be intentionally compromised by altering its morphological integrity. Using a newly developed quantitative assay of invasion we showed that intact CAMs were completely resistant to invasion by tumor cells, wounded CAMs did not pose a barrier to penetration, and CAMs that were wounded and then allowed to reseal displayed partial susceptibility to invasion. The invasion of resealed CAMs required catalytically active plasminogen activator (PA) of the urokinase type (uPA); the invasive efficiency of tumor cells was reduced by 75% when tumor uPA activity or tumor uPA production was inhibited. The invasive ability of human tumor cells, which have surface uPA receptors but which do not produce the enzyme, could be augmented by saturating their receptors with exogenous uPA. The mere stimulation of either uPA or tissue plasminogen activator production, in absence of binding to cell receptors, did not result in an enhancement of invasiveness. These findings suggest that the increased invasive potential of tumor cells is correlated with cell surface-associated proteolytic activity stemming from the interaction between uPA and its surface receptor.

scholarly journals Pericyte–fibroblast transition promotes tumor growth and metastasis

2016 ◽  
Vol 113 (38) ◽  
pp. E5618-E5627 ◽  
Author(s):  
Kayoko Hosaka ◽  
Yunlong Yang ◽  
Takahiro Seki ◽  
Carina Fischer ◽  
Olivier Dubey ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Cancer Metastasis ◽  
Cancer Invasion ◽  
Mouse Strains ◽  
Stromal Fibroblast ◽  
Loss Of Function ◽  
Invasion And Metastasis ◽  
Tumor Dissemination

Vascular pericytes, an important cellular component in the tumor microenvironment, are often associated with tumor vasculatures, and their functions in cancer invasion and metastasis are poorly understood. Here we show that PDGF-BB induces pericyte–fibroblast transition (PFT), which significantly contributes to tumor invasion and metastasis. Gain- and loss-of-function experiments demonstrate that PDGF-BB-PDGFRβ signaling promotes PFT both in vitro and in in vivo tumors. Genome-wide expression analysis indicates that PDGF-BB–activated pericytes acquire mesenchymal progenitor features. Pharmacological inhibition and genetic deletion of PDGFRβ ablate the PDGF-BB–induced PFT. Genetic tracing of pericytes with two independent mouse strains, TN-AP-CreERT2:R26R-tdTomato and NG2-CreERT2:R26R-tdTomato, shows that PFT cells gain stromal fibroblast and myofibroblast markers in tumors. Importantly, coimplantation of PFT cells with less-invasive tumor cells in mice markedly promotes tumor dissemination and invasion, leading to an increased number of circulating tumor cells and metastasis. Our findings reveal a mechanism of vascular pericytes in PDGF-BB–promoted cancer invasion and metastasis by inducing PFT, and thus targeting PFT may offer a new treatment option of cancer metastasis.

scholarly journals In-Vivo Studies of the Angiogenic Potential of Mandur Bhasma

2021 ◽  
pp. 79-84
Author(s):  
Ekta Tomar ◽  
Sonali Wairagade ◽  
Arachana Gharote ◽  
Ranjit S. Ambad ◽  
Dhruba Hari Chandi
Keyword(s):  
Experimental Study ◽  
Analytical Study ◽  
Chorioallantoic Membrane ◽  
In Vivo Studies ◽  
Classical Literature ◽  
Standard Drug ◽  
Angiogenic Potential ◽  
Egg Shell ◽  
Cam Model

Background: Mandur Bhasma is a herbo-mineral compound. It is prepared by Putapaka method. It is described as Raktasanjanan. In the current study, Mandur Bhasma was prepared with a standardized method w.s.r to Rasatarangini and an experimental study was done to observe the Angiogenic property of Mandur Bhasma. The current study will analyze angiogenic potential of Mandur Bhasma using chick CAM model. This research is intended to study the possible role of Mandur Bhasma on angiogenesis and establishing properties of Mandur Bhasma as an angiogenic by newer means. The experimental study inside the egg shell will be carried out on a membrane known as “chorioallantoic membrane”. Objectives: To Prepare Mandur Bhasma Physicochemical and Analytical study of Mandur Bhasma To verify the angiogenic potential of Mandur bhasma using the chicken chorioallantoic membrane (CAM) model. To compare Angeogenic potential of Mandur bhasma with standard drug progesterone Methodology: Relevant classical literature regarding Mandur will be reviewed and the data will be collected. Mandur Shodhan with Gomutra and Mandur Maran with Triphala decoction will be done. Analytical Study like Organoleptic Test for Rasa, Gandha, Varna, Sparsha, Physicochemical Tests and other analytical test like ICP-AES /ICPMS, XRD structure of Bhasma, EDAX-NANO Particle Size will be done. Expected Results: Changes will be observed in objective outcomes. Conclusion: Conclusion will be drawn by suitably analyzing data.

scholarly journals Inhibitory effects of adenovirus mediated Akt1 and PIK3R1 shRNA on the growth of malignant tumor cells in vitro and in vivo

2009 ◽  
Vol 8 (11) ◽  
pp. 1002-1009 ◽  
Author(s):  
Yanchao Fu ◽  
Qingyu Zhang ◽  
Chunsheng Kang ◽  
Jing Zhang ◽  
Kairu Zhang ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Malignant Tumor ◽  
Inhibitory Effects

scholarly journals Proangiogenic role of neutrophil-like inflammatory heterophils during neovascularization induced by growth factors and human tumor cells

Blood ◽  
2006 ◽  
Vol 107 (1) ◽  
pp. 317-327 ◽  
Author(s):  
Andries Zijlstra ◽  
Marco Seandel ◽  
Tatyana A. Kupriyanova ◽  
Juneth J. Partridge ◽  
Mark A. Madsen ◽  
...  
Keyword(s):  
Growth Factors ◽  
Blood Vessel ◽  
Tumor Cells ◽  
Chorioallantoic Membrane ◽  
Human Tumor ◽  
Inflammatory Cells ◽  
Specific Marker ◽  
Matrix Remodeling ◽  
Functional Involvement

Abstract A quantitative in vivo angiogenesis model employing collagen onplants placed on the chick embryo chorioallantoic membrane (CAM) has been used in this study to assess the spatial and temporal associations between neutrophil-like inflammatory cells, namely chicken heterophils, and the development of new blood vessels. Previously we have demonstrated that monocytes/macrophages infiltrating the onplants were associated with extracellular matrix remodeling and angiogenesis, in particular by delivering MMP-13 collagenase. By introducing chicken gelatinase B (chMMP-9) as a specific marker for heterophils, we now show that the onset and extent of angiogenesis induced by purified growth factors or by human HT-1080 fibrosarcoma cells correlated with the initial influx of chMMP-9–positive heterophils. This early heterophil arrival was followed by the infiltration of monocytes/macrophages and appeared to sustain further blood vessel formation. The disruption of inflammatory cell influx by 2 mechanistically distinct anti-inflammatory drugs, cortisone and ibuprofen, significantly inhibited angiogenesis, indicating a functional involvement of these inflammatory cells in new blood vessel development. A direct addition of isolated heterophils or purified chMMP-9 into the HT-1080 onplants engrafted into cortisone- or ibuprofen-treated embryos reversed the antiangiogenic effects of the drugs. The exogenously added heterophils induced in vivo a further infiltration of endogenous heterophils and monocytes and dramatically rescued the impaired angiogenesis, highlighting the importance of early inflammatory leukocytes in tumor-induced angiogenesis. Moreover, purified heterophils incorporated into onplants lacking growth factors or tumor cells induced angiogenesis in nontreated embryos, further indicating a direct proangiogenic role for neutrophil-like leukocytes.

scholarly journals Implementation of the Chick Chorioallantoic Membrane (CAM) Model in Radiation Biology and Experimental Radiation Oncology Research

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1499 ◽  
Author(s):  
Dünker ◽  
Jendrossek
Keyword(s):  
Radiation Oncology ◽  
Current Knowledge ◽  
Treatment Success ◽  
Chorioallantoic Membrane ◽  
Radiation Biology ◽  
Special Focus ◽  
Chick Chorioallantoic Membrane ◽  
Oncology Research ◽  
Cam Model

Radiotherapy (RT) is part of standard cancer treatment. Innovations in treatment planning and increased precision in dose delivery have significantly improved the therapeutic gain of radiotherapy but are reaching their limits due to biologic constraints. Thus, a better understanding of the complex local and systemic responses to RT and of the biological mechanisms causing treatment success or failure is required if we aim to define novel targets for biological therapy optimization. Moreover, optimal treatment schedules and prognostic biomarkers have to be defined for assigning patients to the best treatment option. The complexity of the tumor environment and of the radiation response requires extensive in vivo experiments for the validation of such treatments. So far in vivo investigations have mostly been performed in time- and cost-intensive murine models. Here we propose the implementation of the chick chorioallantoic membrane (CAM) model as a fast, cost-efficient model for semi high-throughput preclinical in vivo screening of the modulation of the radiation effects by molecularly targeted drugs. This review provides a comprehensive overview on the application spectrum, advantages and limitations of the CAM assay and summarizes current knowledge of its applicability for cancer research with special focus on research in radiation biology and experimental radiation oncology.

scholarly journals Rac3 regulates breast cancer invasion and metastasis by controlling adhesion and matrix degradation

2017 ◽  
Vol 216 (12) ◽  
pp. 4331-4349 ◽  
Author(s):  
Sara K. Donnelly ◽  
Ramon Cabrera ◽  
Serena P.H. Mao ◽  
John R. Christin ◽  
Bin Wu ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Initial Step ◽  
Surrounding Tissue ◽  
Matrix Degradation ◽  
Nucleotide Exchange ◽  
Invasion And Metastasis ◽  
Downstream Effector ◽  
Breast Cancer Invasion ◽  
The Matrix

The initial step of metastasis is the local invasion of tumor cells into the surrounding tissue. Invadopodia are actin-based protrusions that mediate the matrix degradation necessary for invasion and metastasis of tumor cells. We demonstrate that Rac3 GTPase is critical for integrating the adhesion of invadopodia to the extracellular matrix (ECM) with their ability to degrade the ECM in breast tumor cells. We identify two pathways at invadopodia important for integrin activation and delivery of matrix metalloproteinases: through the upstream recruiter CIB1 as well as the downstream effector GIT1. Rac3 activity, at and surrounding invadopodia, is controlled by Vav2 and βPIX. These guanine nucleotide exchange factors regulate the spatiotemporal dynamics of Rac3 activity, impacting GIT1 localization. Moreover, the GTPase-activating function of GIT1 toward the vesicular trafficking regulator Arf6 GTPase is required for matrix degradation. Importantly, Rac3 regulates the ability of tumor cells to metastasize in vivo. The Rac3-dependent mechanisms we show in this study are critical for balancing proteolytic activity and adhesive activity to achieve a maximally invasive phenotype.

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