Jacqueline Vink

Role of alpha 3 beta 1 and alpha 2 beta 1 integrins in melanoma cell migration.

Recent findings Indicate that variable expression of β Integrins may play a role In differential melanoma cell motility. Primary melanoma (PM) and metastatic melanoma (MM) cultures, derived from the same patient, were tested for their β1, α2, α3, and α6, Integrln subunlt expression and cell migration on type IV collagen (CN IV) or lamlnln (LN). The MM cell line expressed markedly Increased levels of the β1, α2 and α3, but not α6 subunlt compared to the PM cell line. The MM cell migration rate was significantly higher than that of the PM cell line on LN- or CN IV-coated substrates. Furthermore, the cell migration rate of both lines was significantly higher (p < 0.001) on these substrates than on the control substrates. The MM and PM cell migration was significantly Inhibited by function-blocking antl-β1 and anti-α3 MAbs, but not by the antl-α6 MAb tested. In contrast, the anti-α2 MAb significantly Inhibited MM but not PM cell migration. These data show that the α3 subunlt plays a significant role in melanoma cell motility on CN IV and LN and that. the α3 subunlt has a significant contribution to the motility of the MM cell line.

Actin Organization and Cell Migration of Melanoma Cells Relate to Differential Expression of Integrins and Actin-associated Proteins

We have recently described marked differences in cell migration rates and organization of actin in human melanoma cell lines isolated from various stages of tumor progression. Metastatic lines derived from lymph node metastases organized actin into stress fiber arrays and had high mean migration rates in vitro when compared to lines from other stages. Melanoma cells also reveal marked differences in localization of alpha‐actinin and β1 integrins at stress fiber termination sites (focal contacts). Disruption of this organization is induced by antibodies against β1 integrins. α‐actinin, recently postulated as having a role in linkage of actin to β1 integrins, is differentially expressed in melanoma cells by Northern blot analysis and a relatively high α‐actinin to actin ratio is associated with stress fiber formation and increased cell migration. Furthermore, actin‐binding protein, which cross‐links actin filaments, is also significantly increased in lines exhibiting high migration rates.

Characterization of interleukin-1 alpha-induced melanoma cell motility: inhibition by type I and type II receptor-blocking monoclonal antibodies.

Interleukin-1α (IL-1α) induces cell motility in a variety of benign cell types and in some but not all malignant cell lines in vitro. This study characterizes the IL-1α-induced motility of an aggressive human melanoma cell line that expresses both type I and type II IL-1 receptors. We tested the effect of monoclonal antibodies including function-blocking moAbs against the type I and type II IL-1 receptors on melanoma cell motility to determine which receptor is involved in signal transduction of IL-1α-induced melanoma cell motility. IL-1α significantly increases MM-RU melanoma cell migration in a dose-dependent manner using modified Boyden chamber assays at concentrations 10 to 100 times less than concentrations that significantly inhibit cell growth. Computer-assisted time-lapse image analysis reveals that the motility is inhibited in a dose-dependent manner by neutralizing antibodies against IL-1α. Function-blocking monoclonal antibodies against either type I or type II IL-1 receptors show a significant inhibition of cytokine-induced enhanced cell migration. When both the anti-IL-1 receptor antibodies are added together, the motility response is completely blocked to control levels. Taken together the data indicate that the IL-1α-induced motility of MM-RU melanoma cells is mediated through both type I and type II IL-1 receptors. The significant inhibition of motility by neutralizing IL-1α or blocking either one or both of the IL-1 receptors indicates an integration of IL-1- induced signals in the induction of melanoma cell migration.