Mechanism and biological significance of constitutive expression of MGSA/GRO chemokines in malignant melanoma tumor progression.

Luan J, Shattuck-Brandt R, Haghnegahdar H, Owen JD, Strieter R, Burdick M, Nirodi C, Beauchamp D, Johnson KN, Richmond A
J Leukoc Biol. 1997 62 (5): 588-97

PMID: 9365113 · DOI:10.1002/jlb.62.5.588

By reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemistry, MGSA-alpha, -beta, -gamma, and CXCR2 mRNA expression and proteins are detected in 7 out of 10 human melanoma lesions. The biological consequence of constitutive expression of the MGSA/GRO chemokine in immortalized melanocytes was tested in SCID and nude mouse models. Continuous expression of MGSA/GRO-alpha, -beta, or -gamma in immortalized melan-a mouse melanocytes results in nearly 100% tumor formation for each of the clones tested, whereas clones expressing only the neomycin resistance vector form tumors <10% of the time. Moreover, antibodies to the MGSA/GRO proteins slow or inhibit the formation of tumors in the SCID mouse model and block the angiogenic response to conditioned medium from the tumor-producing clones. Transcription of the MGSA/GRO chemokines is regulated by an enhancesome-like complex comprised of the nuclear factor-kappaB (NF-kappaB), HMG(I)Y, IUR, and Sp1 elements. In Hs294T melanoma cells the half life of the IKB protein is shortened in comparison to normal retinal epithelial cells, facilitating the endogenous nuclear localization of NF-kappaB. We propose that this endogenous nuclear NF-kappaB, working in concert with the 115-kDa IUR-binding factor, promotes constitutive expression of MGSA/GRO genes.

MeSH Terms (11)

Animals Chemokine CXCL1 Chemokines Chemokines, CXC Chemotactic Factors Disease Progression Growth Substances Humans Intercellular Signaling Peptides and Proteins Melanoma Mice

Connections (3)

This publication is referenced by other Labnodes entities:

Links