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Completed

NCT Number: NCT04047459

Investigation of Cancer Cell Extravasation Through mRNA Analysis of Organ-specific Endothelial Cells and Microfluidics

The project aims at unraveling the role of organ-specific endothelia mediating the preferential metastasisation of breast cancer cells to bone by using a multi-faceted approach, integrating microfluidics and transcriptomic profiling. Based on a recently study published by the investigators [Jeon et al., PNAS 2015], it can be hypothesized that phenotypic differences at the level of organ-specific endothelial cells are able to drive the preferential extravasation of breast cancer cells to specific sites. Hence, the transcriptional profile of primary organ-specific endothelial cells derived from healthy patients (i.e. non-affected by breast cancer) will be analyzed to identify phenotypic differences between organ-specific populations of endothelial cells. These analyses will allow to identify potential target genes involved in the organ-specific extravasation of cancer cells (i.e. genes differentially expressed by endothelia of preferential and non-preferential metastasisation sites). The selected genes will be silenced and the effect of gene silencing will be evaluated through microfluidic in vitro organ-specific 3D models designed to study cancer cell extravasation.

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Key information

Conditions

Breast Cancer Metastatic

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Observational

Primary location

IRCCS Galeazzi Orthopedic Hospital

Milan, 20161, Italy

About this study

In particular, the main aim of the study will be to highlight differences between bone and skeletal muscle microenvironments, which are respectively preferential and non-preferential metastasisation sites for breast cancer cells, in order to identify specific pathways driving breast cancer cells extravasation. To this purpose, differences in the transcriptional profile of ECs derived from bone and muscle endothelium will be investigated. These analyses will be used to select target genes differentially expressed by bone- and muscle-specific ECs. Then, ECs obtained from bone and muscle endothelium will be respectively used to mimic bone and muscle microvessel environments in microfluidic in vitro 3D models allowing for the study of breast cancer cell extravasation. The genes selected according to the results of the transcriptomic analysis (e.g. genes expressed in ECs derived from bone endothelium, but not expressed in ECs derived from muscle endothelium) will be silenced and the effect of gene silencing will be evaluated monitoring breast cancer cell extravasation in order to verify the involvement of the selected genes in this process.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • age between 18-65 years
  • patients undergoing cruciate ligament surgery or hip arthroplasty
  • subscription of informed consent

Exclusion criteria

  • HIV, HCV, HBV, TPHA viral

Treatment and study plan

Tissue samples collection and cells isolation

Other

During surgery, leftover samples of bone (femoral head/ trabecular bone tissue) and muscle will be collected. Then they will be sent to the laboratory where isolation of cells will be performed.

Primary outcomes

  1. Genes differentially expressed by bone and muscle ECs

    Time frame: 31/05/2018

    Differential expression of genes will be determined by transcriptomic analysis of mRNA (with genome-wide mRNA array tools) derived from bone and muscle ECs

Secondary outcomes

  1. Differences in adhesive properties of bone and muscle ECs

    Time frame: 31/05/2018

    Bone and muscle derived ECs will be compared in terms of immunofluorescent staining for adhesion molecules (ICAM-1, E-selectin)

  2. Differences in cell adhesion between bone and muscle ECs

    Time frame: 31/05/2018

    Bone and muscle derived ECs will be compared in terms of number of cells adhered (neutrophils, ...)

  3. Differences in angiogenic potential between bone and muscle ECs

    Time frame: 31/05/2018

    Bone and muscle derived ECs will be compared in terms of angiogenic sprouting, by analyzing immunofluorescence images

  4. Selection of potential target genes involved in breast cancer metastasis

    Time frame: 31/05/2018

    Differentially expressed genes potentially involved in breast cancer cells extravasation and metastasis formation

Sponsors and collaborators

Lead sponsor

I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio

Other

Registry information

Official study title

Identification of Novel Genes Involved in Cancer Cell Extravasation by Transcriptional Profiling of Primary Organ-specific Endothelial Cells and in Vitro 3D Models

Important dates

Study start
2016
Primary completion
2018
Study completion
2018
First posted
Aug 6, 2019
Registry last updated
Aug 6, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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