Role of SLURP-1 in Melanoma and Melanoma Stem Cells
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Purpose
Melanoma is the most aggressive skin cancer, with a propensity to metastasize, and is resistant to most of the current therapeutic regimens. Incidence rate of melanoma in patients with MDM (Mal De Maleda, with SLURP-1 mutation) is much higher than normal counterpart. SLURP-1 (lymphocyte antigen 6/urokinase-type plasminogen activator receptor related protein-1) is an allosteric agonist to the nicotinic acetylcholine receptor (nAchR) and it regulates epidermal homeostasis and T-cell function. The preliminary results of comparing human peripheral blood mononuclear cells (PBMCs) from 4 affected and 15 unaffected members from the family with MDM revealed that T-cell activation was impaired in PBMCs with the heterozygous and homozygous SLURP-1 G86R mutation. (2 of affected members developed melanoma.) Since there is currently no effective treatment for metastatic melanoma, identifying novel molecular mechanisms may lead to development of new treatments for metastatic melanomas.
Previous study showed that melanoma stem cells (MSCs) are crucial in melanoma pathogenesis: 1.Melanoma contains ABCB5, CD133 and ABCG2 positive cells had enhanced tumorigenic potential. 2.Higher frequencies of cells capable of initiating melanoma xenografts when using IL2Rγ-/- NOD SCID mice. These data confirmed the interaction between T cells and MSCs.
In this project, we will investigate the roles of SLURP-1 in melanoma and MSCs. Investigating and verifying the interaction between T-cells from patients with MDM and melanoma cells to confirm the SLURP-1 function of tumorigenesis in xenotransplant mice (IL2Rγ-/- NOD SCID) model. To reveal the role of SLURP-1 silencing in melanoma cell lines by using not only A2058 , A375 and MeWo mwlanima cell lines but also ABCB5+ melanoma cells and ABCB5- melanoma cells through the tumorigenesis, apoptosis,angiogenesis, proliferation, melanosphere formation assays.
The aim of this project is to investigate the roles and molecular mechanisms of SLURP-1 in melanoma carcinogenesis, which may improve the development of novel treatments for melanoma.
| Condition |
|---|
|
Melanoma; |
| Study Type: | Observational |
| Study Design: | Observational Model: Case Control Time Perspective: Prospective |
serum, DNA, tissue
| Estimated Enrollment: | 150 |
| Study Start Date: | January 2011 |
| Estimated Study Completion Date: | July 2019 |
| Estimated Primary Completion Date: | July 2014 (Final data collection date for primary outcome measure) |
| Groups/Cohorts |
|---|
|
healthy adults
healthy adults with the age among 20 to 95 years old
|
|
melanoma cases
the people who are diagnosed melanoma in NTU hospital
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 20 Years to 95 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
| Sampling Method: | Probability Sample |
case and control study of melanoma disease
Inclusion Criteria:
- Clinical diagnosis of melanoma Disease by NTU hospital(group of cases)
- healthy adults(groups of control)
Exclusion Criteria:
- two groups whose age are younger than 20 or older tha 95 years old
- Clinical diagnosis of non-melanoma Disease by NTU hospital(group of cases)
Contacts and Locations| Contact: Shiou-Hwa Jee, M.D., Ph.D. | 886-9-72651116 | shiouhwa@gmail.com; shiouhwa@ntu.edu.tw |
| Taiwan | |
| Department of Dermatology, National Taiwan University Hospital. | Recruiting |
| Taipei, Taiwan, 100 | |
| Contact: Shiou-Hwa Jee, M.D., Ph.D. 886-9-72651116 shiouhwa@gmail.com; shiouhwa@ntu.edu.tw | |
| Sub-Investigator: Jung-Ting Kao, M.D. | |
| Study Chair: | Shiou-Hwa Jee, M.D., Ph.D. | Department of Dermatology, National Taiwan University Hospital. |
More Information
No publications provided
| Responsible Party: | Shiou-Hwa Jee, M.D., Ph.D., Professor,Department of Dermatology,National Taiwan University Hospital |
| ClinicalTrials.gov Identifier: | NCT01281722 History of Changes |
| Other Study ID Numbers: | 201012044RB |
| Study First Received: | January 20, 2011 |
| Last Updated: | January 21, 2011 |
| Health Authority: | Taiwan: Department of Health |
Keywords provided by National Taiwan University Hospital:
|
healthy adults melanoma |
Additional relevant MeSH terms:
|
Melanoma Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal |
Neoplasms by Histologic Type Neoplasms Neoplasms, Nerve Tissue Nevi and Melanomas |
ClinicalTrials.gov processed this record on May 23, 2013