Role of Toll-like receptors in pro-tumor role of mesenchymal stromal cells from patients with chronic myeloid leukemia (CML)
Universita degli Studi di Catania
Division of Hematology, Az. Ospedaliero- Universitaria Policlinico, via Santa Sofia, 86, CAP 95123, University of Catania, Catania, Italy
Dott.ssa Cesarina Giallongo, dott. DanieleTibullo,
Dott.ssa Cesarina Giallongo, dott. DanieleTibullo,
English (B2); Italian
4 weeks
Cities/Months Jan Feb Mar Apr May Jun Jul Augt Sep Oct Nov Dec
No No No No No No No Yes No No No No
Type of Research Project
- Clinical Project with Laboratory work
What is the background of the project?
The functional mesenchymal stem cells (MSC) behavior is essential to favor or impede leukemic stem cells (LSC) expansion and for this reason MSC represent a possible target to treat leukemias .MSC also play an important role for their immunosuppressive ability that can interfere with the immune recognition of tumor cells. In breast cancer, MSC protect tumor cells by increasing T-regs and decreasing the activity of natural killer cells and cytotoxic T lymphocytes, which are responsible for tumor cell destruction. Since a connection between the stimulation of specific Toll-like receptors (TLR) and MSC activation status has been demonstrated, we hypothesize that the tumor-promoting phenotype of CML-MSC may be associated to TLRs, that are type-I transmenbrane glycoproteins that recognize ‘‘danger’’ signals leading to profound cellular and systemic responses that mobilize innate and adaptive host immune cell. MSC express several TLR and their ability to migrate, invade and secrete immune modulating factors is drastically affected by specific TLR-agonist engagement. MSC can polarize into two different types with distinct phenotypes defined MSC1 and MSC2.
What is the aim of the project?
The aim of this project is to identify molecular pathways which are able to activate the pro-tumoral phenotype of MSC in order to inhibit interactions among LSC and stromal components promoting immune escape and tumor growth.
What techniques and methods are used?
- Cell culture techniques and analysis of transcriptome databases are used, especially on involted stem cells. - Flow cytometry will be used to detect and measure physical and chemical characteristics of leukemic stem cells. - To analyze the different molecular pathways and the two phenotypes of mesenchymal stem cells MSC1 and MSC2, RT-PCR (Reverse transcriptase-polymerase chain reaction) is used: In RT-PCR, the RNA template is first converted into a complementary DNA (cDNA) using a reverse transcriptase. The cDNA is then used as a template for exponential amplification using PCR for gene expression. -To better understand different receptors pathways the serum samples of patients with chronic myeloid leukemia are collected and analyzed even through ELISA (Enzyme-Linked Immuno Sorbent assay).
What is the role of the student?
- The student will mainly observe
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- If the project includes “lab work”
- the student will take active part in the practical aspect of the project
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
The student is supposed to attend regularly the research internship, to be cooperative. It will be important to participate willingly to the activities, maybe giving new point of view to the tutor. Students will follow the entire process of the experiments and will be able with time to conduct experiment by him/herself. In addition students could follow the ward and outpatients activity and could be able to integrate information coming from the lab with clinical features of the patients
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- No specific outcome is expected
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts:
- Medical students
- Graduated students (less than 6 months)
- Pre-Medical students from the American-British system
- Giallongo C; Parrinello N; Tibullo D; La Cava P; Romano A; Chiarenza A; et al. Myeloid derived suppressor cells (MDSCs) are increased and exert immunosuppressive activity together with polymorphonuclear leukocytes (PMNs) in chronic myeloid leukemia patients. PloS one. 2014;9(7):e101848. PubMed PMID: 25014230. Pubmed Central PMCID: 4094386.