Inverse relationship between invasiveness and differentiative capacity in different human neuroblastoma cell lines

Abstract

In order to clarify the relationship between invasiveness and loss of cellular differentiation in tumor cells, we studied the invasive properties on Matrigel of (a) a series of clones we isolated from human neuroblastoma LaN1 and Platt cell lines inducible to differentiation by adhesion on fibronectin, and (b) SY5Y human neuroblastoma cells inducible to differentiation by retinoic acid. We found that, regardless of the parental line, the more differentiated clones were scarcely invasive, while the less differentiated clones showed a higher degree of invasiveness. Differences in invasiveness between differentiated and non-differentiated neuroblastoma clones did not reflect differences in adhesiveness to laminin, the major component of Matrigel. The retinoic acid-sensitive SY5Y human neuroblastoma cells also reduced their invasiveness on Matrigel after differentiation induced by growth in media supplemented with retinoic acid. These results point to an inverse relationship between differentiative properties and invasiveness in human neuroblastoma cell lines.

Platelet Activating Factor Inhibits the Expression of Matrix Metalloproteinases and Affects Invasiveness and Differentiation in a System of Human Neuroblastoma Clones

“…According to the results reported in a previous paper (Barletta et al, 1997), clone AE12 expressed a low level of differentiation, as shown by the small percentage of cells with neurites (7% of cells with neurites), while a higher level of differentiation was shown by clone AA5 (18% of cells with neurites) ( Figure 5). Moreover, when invasion through Matrigel was investigated (Figure 6), the less differentiated AE12 clone showed a higher rate of invasiveness than the well-differentiated AA5 clone, as reported in a previous paper (Barletta et al, 1997).…”

“…The use of metalloproteinase inhibitors in the control of tumor invasion and metastasis has also entered in the routine of cancer therapy (Giavazzi and Taraboletti, 2001). In the present study, we investigated the role of PAF in differentiation and invasiveness by the use of an experimental model represented by two neuroblastoma clones, AA5 and AE12, with a different degree of invasiveness and differentiation (Barletta et al, 1997). In the present study, we investigated the role of PAF in differentiation and invasiveness by the use of an experimental model represented by two neuroblastoma clones, AA5 and AE12, with a different degree of invasiveness and differentiation (Barletta et al, 1997).…”

“…In particular, matrix metalloproteinases (MMPs), a well-characterized group of neutral peptidases secreted by malignant cells, are re-tive (72 kDa), and active (64 kDa), forms of MMP-2 (Figure 1A), a result that was confirmed by the Western blot analysis of conditioned media ( Figure 1C). Densitometric evaluation of zymographs indicated higher levels of both inactive and active MMP-2 in the less differentiated and more invasive AE12 clone compared to the well-differentiated AA5 clone (Barletta et al, 1997) (Figure 1B). Densitometric evaluation of zymographs indicated higher levels of both inactive and active MMP-2 in the less differentiated and more invasive AE12 clone compared to the well-differentiated AA5 clone (Barletta et al, 1997) (Figure 1B).…”

“…These clones were at the extremes of a series of clones isolated from the human LaN1 neuroblastoma cell line, in which the differentiative capacities were inversely correlated with invasiveness (Barletta et al, 1997). These clones were at the extremes of a series of clones isolated from the human LaN1 neuroblastoma cell line, in which the differentiative capacities were inversely correlated with invasiveness (Barletta et al, 1997).…”

Expressions of URG4/URGCP, cyclin D1, Bcl-2 , and Bax genes in retinoic acid treated SH-SY5Y human neuroblastoma cells

“…Additionally, it is discussed that the dramatically different response to RA is dependent on the tumor stage of the patient. Thus, aggressive and spreading tumor cells could be transformed in vitro to mature and non-proliferating cells [9, 10]. …”