Recombinant expression, biochemical characterization and biological activities of the human MGSA/gro protein

Abstract

Melanoma growth stimulatory activity (MGSA) is a mitogenic protein secreted by Hs294T melanoma cells that corresponds to the polypeptide encoded by the human gro gene. The MGSA/gro cDNA has been expressed in mammalian cells and the secreted recombinant factor has been purified. Biochemical and biological characterization shows that the recombinant protein is identical with the natural protein and is devoid of posttranslational glycosylation, sulfation, and phosphorylation. The two C-terminal amino acids are proteolytically removed from the mature recombinant MGSA, indicating a length of 71 instead of the predicted 73 amino acids. The recombinant MGSA is mitogenically active on the Hs294T melanoma cells. The purified MGSA competes with interleukin 8 for binding to neutrophil receptors and exhibits neutrophil chemotactic activity equivalent to that of interleukin 8.

Melanoma Growth Stimulatory Activity in Primary Malignant Melanoma: Prognostic Significance

“…Purified MGSA, initially identified as a factor secreted by the human melanoma cell line Hs294T, was found to have the ability to mitogenically stimulate these same melanoma cells (8). Later, purified recombinant MGSA was found to be mitogenically active on melanoma cells in vitro (4).…”

“…Human umbilical vein endothelial cells are capable of synthesizing and secreting MGSA (20). This expression is also shown to be strongly induced by factors involved in inflammation and to exhibit neutrophil chemotactic activity (4). An increase in vascularity is associated with tumor progression in melanocytic lesions from benign melanocytic nevi to MM (21).…”

“…MGSA is one of a number of biologically active cytokines that have been localized to the skin (3). It is a mitogenic protein secreted by melanoma cell lines and corresponding to the polypeptide encoded by the human GRO gene (4). MGSA GRO␣ is a 73-amino acid peptide sharing sequence characteristics with the ␣-chemokine superfamily.…”

Infiltration of neutrophils by intrapleural injection of tumour necrosis factor, interleukin‐1, and interleukin‐8 in rats, and its modification by actinomycin D

“…shown to have higher homology to human MGSA/gro, which is a member of the chemokine family and also a neutrophil chemoattractant (Derynck et al, 1990), than to IL-8. Although several studies demonstrated that IL-8 Ribeiro et al, 1991;Rot, 1991) and CINC (Watanabe et al, 1991;Hirasawa et al, 1992) induced neutrophil infiltration in rats in vivo, there is, to our knowledge, no report comparing the neutrophil chemotactic activity of CINC and IL-8 in the same inflammatory model in rats.…”

Glucocorticoid-mediated Gene Suppression of Rat Cytokine-induced Neutrophil Chemoattractant CINC/gro, a Member of the Interleukin-8 Family, through Impairment of NF-κB Activation

“…In addition to these, we found a novel polypeptide neutrophil chemotactic factor, cytokine-induced neutrophil chemoattractant (CINC), 1 which is produced by the normal rat kidney epithelial cell line NRK-52E (3,4). According to its amino acid sequence, CINC appears to be a member of the human cytokine family that includes interleukin-8 (IL-8) and three closely related gro gene products, GRO␣ , GRO␤, and GRO␥ (melanoma growth-stimulating activity ␣, ␤, and ␥, respectively), all of which have chemotactic activities for human neutrophils (5)(6)(7)(8).…”