A motogén szignál vizsgálata humán melanómasejtekben

Translated title of the contribution: Investigation of the motogenic signal in human melanoma cells

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The components of the extracellular matrix (ECM) are more than just adhesion sites for migrating tumor cells: following enzymatic degradation of the ECM, the release of sequestrated growth factors increases, thus they become available for tumor cells. In a number of cancers dysfunction of epidermal growth factor receptor (EGFR) or hepatocyte growth factor receptor (c-Met) contribute to the malignant transformation that directly regulates cell proliferation, survival and motility. Furthermore, intracellular calcium level plays an important role in the regulation of the tyrosine kinase pathway. In our preclinical experiments, by administering heparin-derived oligosaccharides we influenced the interaction between human melanoma cells and ECM. In vitro cell migration was inhibited by heparin fragments. Moreover, two of the effective oligosaccharides reduced the number of lung colonies formed in SCID mice. In human melanoma cells an important element of Ca2+ homeostasis, the purinergic Ca2+ channel P2X7 proved to be an anti-apoptotic protein. EGFR and c-Met showed constitutive activity in human melanoma cells, and their inhibition in vitro caused decreased proliferation, migration and elevated apoptosis. Administration of a selective c-Met-TKI significantly decreased primary tumor growth in vivo as well as the capacity for liver colony formation in SCID mice. Selective EGFR-TKI had less inhibitory effect on metastasis formation, and had no effect on the primary tumor. Our results suggest the necessity of a rational dual-specific drug design for the purpose in the therapy of malignant melanoma.

Original languageHungarian
Pages (from-to)55-58
Number of pages4
JournalMagyar Onkologia
Volume55
Issue number1
Publication statusPublished - 2011

Fingerprint

Melanoma
Epidermal Growth Factor Receptor
Extracellular Matrix
SCID Mice
Neoplasms
Oligosaccharides
Cell Movement
Heparin
Proto-Oncogene Proteins c-met
Apoptosis Regulatory Proteins
Drug Design
Human Activities
Protein-Tyrosine Kinases
Cell Survival
Intercellular Signaling Peptides and Proteins
Homeostasis
Cell Proliferation
Apoptosis
Neoplasm Metastasis
Calcium

ASJC Scopus subject areas

  • Oncology

Cite this

A motogén szignál vizsgálata humán melanómasejtekben. / Kenessey, I.

In: Magyar Onkologia, Vol. 55, No. 1, 2011, p. 55-58.

Research output: Contribution to journalArticle

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