Tumor‐associated alpha‐2‐macroglobulin in human melanomas

Abstract

We and others have previously shown that human melanoma cell lines in culture synthesize alpha-2-macroglobulin (alpha 2M). We have now studied melanomas from 30 patients for the presence of alpha 2M using the peroxidase anti-peroxidase technique on histologic sections from paraffin-embedded tissues and primary antibody raised against tumor-associated alpha 2M in rabbits. alpha 2M was detected in 10 of the 30 melanomas studied. In all but 2 cases the presence of alpha 2M was restricted to solitary tumor cells or to solitary foci of tumor tissue. In one case of melanoma almost all tumor cells were positive for alpha 2M, while in the others between 20% and 50% of tumor cells were positive. In all but one of the melanomas, the positivity was characteristic of epithelioid or large-cell type or was confined to this component in melanomas with more than one cell type. In 4 positive cases, differences in the extent of alpha 2M-containing tumor tissue were observed between primary tumor and metastases or metastases from different localizations, with equivocal trend. Clinical follow-up of the melanoma patients suggested that alpha 2M-positively tends to correlate with an unfavorable prognosis.

Establishment of a new human cancer cell line secreting protease nexin‐II/amyloid β protein precursor derived from squamous‐cell carcinoma of lung

“…Moreover, immunohistochemical studies have suggested a poor prognosis for patients with a,-AT-, a,-MG-and PSTI-rich tumors (Tahara et al, 1984;Matoska et al, 1988;Higashiyama et ab, 1990). Immunohistochemically, the incidence of a,-AT is markedly higher in advanced colorec-LC-l/sq.…”

Role of zinc and α2macroglobulin on thymic endocrine activity and on peripheral immune efficiency (natural killer activity and interleukin 2) in cervical carcinoma

“…Moreover, this protective role of α 2 -macroglobulin may further justify the shift of zinc towards this metalloprotein in cervical carcinoma. On the other hand, increases in α 2 -macroglobulin have been also found in tumour experimental models (Mackiewicz et al, 1993) and in melanoma patients, although such increments were associated with unfavourable prognosis (Matoska et al, 1988). This is not surprising because the shift of zinc results in a low zinc bioavailability with consequent reduction in peripheral thymulin molecules saturated by zinc ions, resulting in reduced zinc-bound active thymulin and impairment of immune efficiency against tumours.…”

“…In this context, α 2 -macroglobulin may play a key role for two reasons: firstly, because of a high K d for zinc (10 -10 M) (Giroux, 1975) and, secondly, because α 2 -macroglobulin is implicated as an inhibitor of matrix metalloproteases (MMPs) (Enghild et al, 1989) against invasive tumour proliferation ( Stetler-Stevenson et al, 1993). Indeed, increases in α 2 -macroglobulin have been reported in experimental neoplasia (Mackiewicz et al, 1993) and in melanoma patients (Matoska et al, 1988). Therefore, we measured plasma levels of zinc, of active thymulin (Zn-FTS) and of α 2 -macroglobulin in patients affected by locally advanced cervical carcinoma.…”

Synthesis and secretion of α2-macroglobulin by human glioma established cell lines

“…In this connection, a bad prognosis has been suggested for patients with ~2M containing tumors (Tahara et al 1984;Matoska et al 1988;Kataoka et al 1989).…”