Hayashi S, Kurdowska A, Cohen A B, Stevens M D, Fujisawa N, Miller E J
Department of Biochemistry, University of Texas Health Center at Tyler, Tyler, Texas 75710, USA.
J Clin Invest. 1997 Jun 1;99(11):2581-7. doi: 10.1172/JCI119446.
Melanoma growth stimulatory activity (MGSA/GROalpha) is a 73 amino acid peptide sharing sequence characteristics with the alpha-chemokine superfamily. MGSA/GROalpha is produced by diverse melanoma cell lines and reported to act as an autocrine growth factor for the cells. We tested the binding of MGSA/GROalpha to melanoma cell lines, Hs 294T and RPMI7951, and found that these cells could bind to MGSA/GROalpha but not to interleukin-8. Recently, we defined a novel hexapeptide, antileukinate, which is a potent inhibitor of binding of alpha-chemokines to their receptors on neutrophils. When antileukinate was added to melanoma cells, it inhibited the binding of MGSA/ GROalpha. The growth of cells from both melanoma cell lines was suppressed completely in the presence of 100 microM peptide. The cell growth inhibition was reversed by the removal of the peptide from the culture media or by the addition of the excess amount of MGSA/GROalpha. The viability of Hs 294T cells in the presence of 100 microM peptide was > 92%. These findings suggest that MGSA/GROalpha is an essential autostimulatory growth factor for melanoma cells and antileukinate inhibits their growth by preventing MGSA/GROalpha from binding to its receptors.
黑色素瘤生长刺激活性因子（MGSA/GROα）是一种由73个氨基酸组成的肽，与α趋化因子超家族具有共同的序列特征。MGSA/GROα由多种黑色素瘤细胞系产生，并据报道可作为这些细胞的自分泌生长因子。我们检测了MGSA/GROα与黑色素瘤细胞系Hs 294T和RPMI7951的结合情况，发现这些细胞能够与MGSA/GROα结合，但不能与白细胞介素-8结合。最近，我们确定了一种新型六肽——抗白血病肽，它是α趋化因子与中性粒细胞上其受体结合的有效抑制剂。当将抗白血病肽添加到黑色素瘤细胞中时，它会抑制MGSA/GROα的结合。在存在100微摩尔肽的情况下，来自这两种黑色素瘤细胞系的细胞生长被完全抑制。通过从培养基中去除肽或添加过量的MGSA/GROα，细胞生长抑制作用得以逆转。在存在100微摩尔肽的情况下，Hs 294T细胞的活力>92%。这些发现表明，MGSA/GROα是黑色素瘤细胞必不可少的自刺激生长因子，而抗白血病肽通过阻止MGSA/GROα与其受体结合来抑制它们的生长。
