PUBLICATION
Zebrafish modeling reveals that SPINT1 regulates the aggressiveness of skin cutaneous melanoma and its crosstalk with tumor immune microenvironment
- Authors
- Gómez-Abenza, E., Ibáñez-Molero, S., García-Moreno, D., Fuentes, I., Zon, L.I., Mione, M.C., Cayuela, M.L., Gabellini, C., Mulero, V.
- ID
- ZDB-PUB-190915-1
- Date
- 2019
- Source
- Journal of experimental & clinical cancer research : CR 38: 405 (Journal)
- Registered Authors
- Mione, Marina, Mulero, Victor, Zon, Leonard I.
- Keywords
- Epithelial to mesenchymal transition, Inflammation, Macrophages, Melanoma, Metastasis, SPINT1, Tumor stroma, Zebrafish
- MeSH Terms
-
- Allografts
- Animals
- Biomarkers
- Biopsy
- Cell Communication*
- Disease Models, Animal
- Disease Progression
- Gene Expression
- Gene Knockout Techniques
- Heterografts
- Humans
- Immunomodulation
- Immunophenotyping
- Macrophages/immunology
- Macrophages/metabolism
- Melanoma/etiology*
- Melanoma/metabolism*
- Melanoma/mortality
- Melanoma/pathology
- Prognosis
- Proteinase Inhibitory Proteins, Secretory/genetics*
- Proteinase Inhibitory Proteins, Secretory/metabolism
- Skin Neoplasms/etiology*
- Skin Neoplasms/metabolism*
- Skin Neoplasms/mortality
- Skin Neoplasms/pathology
- Tumor Microenvironment/immunology*
- Zebrafish
- PubMed
- 31519199 Full text @ J. Exp. Clin. Cancer Res.
Citation
Gómez-Abenza, E., Ibáñez-Molero, S., García-Moreno, D., Fuentes, I., Zon, L.I., Mione, M.C., Cayuela, M.L., Gabellini, C., Mulero, V. (2019) Zebrafish modeling reveals that SPINT1 regulates the aggressiveness of skin cutaneous melanoma and its crosstalk with tumor immune microenvironment. Journal of experimental & clinical cancer research : CR. 38:405.
Abstract
Background Skin cutaneous melanoma (SKCM) is the most lethal form of skin cancer and while incidence rates are declining for most cancers, they have been steadily rising for SKCM. Serine protease inhibitor, kunitz-type, 1 (SPINT1) is a type II transmembrane serine protease inhibitor that has been shown to be involved in the development of several types of cancer, such as squamous cell carcinoma and colorectal cancer.
Methods We used the unique advantages of the zebrafish to model the impact of Spint1a deficiency in early transformation, progression and metastatic invasion of SKCM together with in silico analysis of the occurrence and relevance of SPINT1 genetic alterations of the SKCM TCGA cohort.
Results We report here a high prevalence of SPINT1 genetic alterations in SKCM patients and their association with altered tumor immune microenvironment and poor patient survival. The zebrafish model reveals that Spint1a deficiency facilitates oncogenic transformation, regulates the tumor immune microenvironment crosstalk, accelerates the onset of SKCM and promotes metastatic invasion. Notably, Spint1a deficiency is required at both cell autonomous and non-autonomous levels to enhance invasiveness of SKCM.
Conclusions These results reveal a novel therapeutic target for SKCM.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping