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

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

Status: Completed

Conditions: Breast Cancer Metastatic

Treatments: Other: Tissue samples collection and cells isolation

Study type: Observational

Funder types: Other

Identifiers

NCT04047459

BRCP USA

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 31 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

31 participants in 1 patient group

Patient undergoing prosthetic surgery

Description:

Patients undergoing surgery for the insertion of a hip prosthesis or a cruciate ligament reconstruction will be included. On those patients tissue samples collection and cells isolation will be performed

Treatment:

Other: Tissue samples collection and cells isolation