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Activated leucocyte cell adhesion molecule (ALCAM) role in Ewing sarcoma
Spain (IFMSA Spain) - University of Sevilla, Sevilla
Department of Pathology
Prof. Enrique de Alava
Prof. Enrique de Alava, Dr. Ana-Teresa Amaral.
Type of Research Project
- Clinical Project with Laboratory work
What is the background of the project?
The activated leucocyte cell adhesion molecule (ALCAM) or CD166, is a cell surface membrane receptor directly implicated in the transmigration of leukocytes. Expression of ALCAM on the cell surface of endothelial cells is regulated by miR126-5p and is key in the dynamics of leukocyte adhesion-transmigration. ALCAM is typically expressed in mesenchymal stem cells, the most probable cell of origin of Ewing Sarcoma (ES), an aggressive sarcoma of childhood and adolescence. Moreover, ALCAM and the soluble form of ALCAM (sALCAM), were previously described as essential for the balance between cell clustering - cell migration in solid tumors such as prostate cancer, melanoma and ovarian cancer. Shedding of ALCAM from the cell membrane is primarily regulated by ADAM17, also overexpressed in these tumors. Also, paracrine sALCAM stimulation has been described as a determinant factor in metastasis formation via MMP2 inhibition. Our preliminary results show that most of ES cell lines present a strong expression of CD166 when compared to mesenchymal stem cells (MSCs).
What is the aim of the project?
To test the role of ALCAM on the invasive capacity of sarcoma cells, and its possible prognostic and predictive value.
What techniques and methods are used?
Screening of ALCAM/miR126-5p/ADAM17/MMP2 levels in a panel of sarcoma cell lines Study of possible correlation of ALCAM over expression in clinical samples and poor prognosis in Ewing sarcoma. Bioinformatics evaluation of molecular pathways identifying the molecules directly related with ALCAM, through IPA (Ingenuity Pathway Analysis) or similar software. Screening of protein expression and localization of ALCAM in the previous panel of cell lines by Fluorescence-Activated Cell Sorter (FACS) and Immunofluorescence. Transient inhibition of ALCAM expression by siRNA (small interfering ribonucleic acid). Generation of stable ALCAM-silenced cell lines through a lentiviral RNA smart vector (shRNA). Evaluation of the effects on cell proliferation, apoptosis induction, and invasion/migration capacity in ES cells knocked down for ALCAM; Generation of stable miR126-5p-silenced cell lines through a lentiviral RNA smart vector (shRNA) (ES, breast cancer and non-tumoral cell lines). Functional studies focused on the effects on cell clustering/invasion in miR126-5p silenced cells.
What is the role of the student?
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
The student will mainly attend the lab work and labmeetings (the student will interpret the results, see how the research is developed, etc.) , and will get involved in project result discussions. The student will also be involved in the clinical work at the Pathology department, taking place on the different techniques used in our department.
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?
- The student will prepare a poster - The student will prepare a presentation - The student will prepare a scientific report - The student will prepare an abstract - The student’s name will be mentioned in a future publication - The student will have the opportunity to present the results together with the supervisor at a conference
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
A Medical student with both interest in the research and clinical aspects of medicine, with an initial interest in Pathology. Capacity of interaction and communication skills. Active and positive attitude. Subjects passed: Anatomical Pathology Legal limitations: all access to clinical/medical/lab information is confidential
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students
- 1. Postel-Vinay; S.; et al.; Common variants near TARDBP and EGR2 are associated with susceptibility to Ewing sarcoma. Nat Genet; 2012. 44(3): p. 323-7.
- 2. Amaral; A.T.; et al.; Innovative therapies in Ewing Sarcoma. Adv Anat Pathol; 2014. 21(1): p. 44-62.
- 3. Poissonnier; L.; et al.; miR126-5p repression of ALCAM and SetD5 in endothelial cells regulates leucocyte adhesion and transmigration. Cardiovasc Res; 2014. 102(3): p. 436-47.
- 4. Amaral; A.T.; et al.; Characterization of human mesenchymal stem cells from ewing sarcoma patients. Pathogenetic implications. PLoS One; 2014. 9(2): p. e85814.
- 5. Hansen; A.G.; et al.; ALCAM/CD166 is a TGF-beta-responsive marker and functional regulator of prostate cancer metastasis to bone. Cancer Res; 2014. 74(5): p. 1404-15.
- 6. Kahlert; C.; et al.; Increased expression of ALCAM/CD166 in pancreatic cancer is an independent prognostic marker for poor survival and early tumour relapse. Br J Cancer; 2009. 101(3): p. 457-64.
- 7. Rosso; O.; et al.; The ALCAM shedding by the metalloprotease ADAM17/TACE is involved in motility of ovarian carcinoma cells. Mol Cancer Res; 2007. 5(12): p. 1246-53.
- 8. Sadikovic; B.; et al.; Immunohistochemical expression and cluster analysis of mesenchymal and neural stem cell-associated proteins in pediatric soft tissue sarcomas. Pediatr Dev Pathol; 2011. 14(4): p. 259-72.
- 9. van Kempen; L.C.; et al.; Molecular basis for the homophilic activated leukocyte cell adhesion molecule (ALCAM)-ALCAM interaction. J Biol Chem; 2001. 276(28): p. 25783-90.
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