Coexpression of tumor‐associated α₂‐macroglobulin and growth factors in human melanoma cell lines

Abstract

alpha 2-Macroglobulin (alpha 2M) is known as an inhibitor of various proteinases and to bind several of the growth factors. We previously demonstrated that clonal variation exists in the production of alpha 2M in a human melanoma and that this variation may be associated with growth stimulation. We have now analyzed six human melanoma cell lines for the simultaneous expression of TGF-alpha, TGF-beta, PDGF-A chain, PDGF-B chain, and tumor-associated alpha 2M. In Northern blot analysis TGF-alpha was detected in four of the cell lines, TGF-beta in all, PDGF-A chain in three, and PDGF-B chain in none of the cell lines. alpha 2M, detected by immunoblotting, varied significantly between the different melanoma cell lines and only one cell line was found to be negative. Evaluation of growth-promoting activity in conditioned media suggested that alpha 2-macroglobulin, secreted by these tumor cell lines, is a significant modulator of melanoma cell growth.

Profiles of Plasma Serpins in Patients with Advanced Malignant Melanoma, Gastric Cancer and Breast Cancer

“…Other investigators previously found · 2 -M to be markedly increased in patients with advanced gastrointestinal cancer [15]. It was also postulated that · 2 -M is a modulator of melanoma cell growth [25]. In our study we did not observe any significant differences in · 2 -M levels between malignant melanoma patients and healthy controls.…”

Induction of Hepatocyte Growth Factor/Scatter Factor by Fibroblast Clustering Directly Promotes Tumor Cell Invasiveness

“…Because of their high numbers within the tumor mass, stromal fibroblasts are prime targets for tumor-derived paracrine mediators such as growth factors and cytokines. We and others have shown that tumor cells such as melanoma cells produce soluble mitogenic factors for fibroblasts (4,5) that may contribute to fibroblast hyperplasia and reactive stroma within and around growing tumors (6,7). Stromal contributions have been strongly linked to cancer progression, metastasis, and growth (ref.…”

Active transforming growth factor-β in human melanoma cell lines: No evidence for plasmin-related activation of latent TGF-β

“…Three of these isoforms, TGF-P1, -p2, and -03, with similar but not identical biological activities, have been found in mammalian cells [Massague,199Oj. Earlier studies, analyzing TGF-p either at mRNA or protein level, have reported the presence of the growth factor in human melanoma cells Lizonova et al, 1990;Rodeck et al, 19911. In a more detailed study it has been shown that cultured human melanoma cells express constitutively all three TGF-P isoforms [Albino et al, 19911.…”