Recombinant interferon alpha and gamma modulate the invasive potential of human melanoma in vitro

Abstract

We have studied the effects of interferons (IFNs) on the attachment, collagenase IV activity, chemotactic migration and in vitro invasion of human melanoma (A2058) cells treated for various time periods with human recombinant interferon alpha (hrIFN-alpha) or gamma (hrIFN-gamma). The cells treated with hrIFN alpha for a short time period attached more readily to purified basement membrane components, type IV collagen and laminin, than control cells. The stimulating effect of hrIFN gamma on the attachment was seen, however, when the cells were treated for a longer period of time (3 days) with this drug. The short-term treatment with hrIFN alpha also enhanced the in vitro invasion of cells through a reconstituted basement membrane compared to findings with untreated control cells. Pre-treatment of 3 days or more was, however, needed for hrIFN gamma to promote the invasion of A2058 cells. Both IFNs increased the secretion of basement membrane (type IV) collagen degrading metalloproteinase (collagenase IV) activity from human melanoma cells. Further, chemotaxis, i.e., directed migration of A2058 cells to laminin, was enhanced by both IFNs. In contrast, the attachment, collagenase IV activity, chemotaxis, and in vitro invasion were markedly inhibited when the cells were treated for an extended time period (7 days) with the IFNs. Interferons also inhibited cell proliferation after 4 days of exposure. These results suggest that time of treatment with interferons modulates the invasive capacity of human melanoma cells in vitro, causing initially a transient enhancement of invasion followed by an inhibition of invasive propensity after extended exposure to these drugs, and that different biochemical steps required for successful invasion are regulated in parallel by interferons alpha and gamma.

In vitro Comparative Study of the Antitumor Effects of Human Interferon‐α, β and γ on the Growth and Invasive Potential of Human Melanoma Cells

“…It is known that serum concentrations of HuIFN-{3 are not detectable when it is locally administered. However, in lesional lymph nodes, high concentrations (200 to 1000 IV/g) of HuIFN-{3 were verified (20). It is expected that the local administration of HuIFN-{3 has antitumor effects against not only the primary lesion but also the lesionallymph nodes.…”

Interferon‐γ inhibits extravillous trophoblast cell invasion by a mechanism that involves both changes in apoptosis and protease levels

“…MMP2 and MMP9 have been suggested to be the major proteases used by EVT during the invasive process (38). IFN‐γ inhibits the invasiveness of several different cancer cell lines, including astrogliomas U251‐MG and CRT (30), renal cell carcinoma KG2 (31, 32), and melanoma A2058 (33), via a decrease in MMP2 activity. Furthermore, Karmakar et al .…”

Matrix metalloproteinase-2 (MMP-2) immunoreactive protein?a new prognostic marker in uveal melanoma?

“…18 In a human skin melanoma cell line, MMP-2 has been linked to in vitro invasion. 5,28 We recently showed the association of MMP-2 protein to haematogenous metastasis and poor prognosis in skin melanoma. 15,21 Intracytoplasmic staining for MMP-2 protein was found here in uveal melanoma cells.…”