Publication: MIA - a new target protein for malignant melanoma therapy
Authors
Schmidt, Jennifer ; Riechers, Alexander ; Bosserhoff, Anja-Katrin
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Publisher
F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Malignant melanoma, a malignancy of
pigment producing cells, causes the greatest number of
skin cancer-related deaths worldwide. The tumor is
characterized by its aggressive phenotype and can
metastasize at very early stages of the disease. Since
metastatic lesions are usually characterized by an
intrinsic resistance to standard radiation and
chemotherapy, the prognosis of this tumor remains very
poor in advanced stages.
Melanoma inhibitory activity (MIA), an 11 kDa
protein expressed and secreted by melanoma cells after
their malignant transformation, is known to play a key
role in melanoma development, progression and tumor
cell invasion. After its secretion, which is restricted to
the rear pole of migrating cells, MIA protein directly
interacts with cell adhesion receptors and extracellular
matrix molecules. By this mechanism, MIA protein
actively facilitates focal cell detachment from
surrounding structures at the cell rear and strongly
promotes tumor cell invasion and formation of
metastases. It has further been demonstrated that MIA
contributes to immunosuppression frequently seen in
malignant melanomas by binding to integrin α4ß1
expressed by leukocytes and thus inhibiting cellular
antitumor immune response. Analyses at the molecular
level revealed that MIA protein reaches functional
activity by self assembly. Functional inactivation of MIA
protein by dodecapeptides that directly bind to the
dimerization interface leads to a strongly reduced tumor
cell invasion in an in vivo mouse melanoma model. The
molecular understanding of the contribution of MIA
protein to formation of metastases provides an excellent
starting point for the development of a new strategy in
malignant melanoma therapy.
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Citation
Histology and histopathology, Vol. 28, n.º 4 (2013)
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