Autocrine Growth Regulation of CD30 Ligand in CD30-Expressing Reed-Sternberg Cells: Distinction Between Hodgkin's Disease and Anaplastic Large Cell Lymphoma

Abstract

SUMMARY:Persistent expression of high levels of CD30 in Hodgkin's Reed-Sternberg (H-RS) cells and anaplastic large-cell lymphoma (ALCL) cells, but not in most T-or B-cell lymphomas, suggests the presence of an underlying mechanism leading to the abnormality and possible involvement of CD30 in the growth and survival of these two unique types of tumors. In this study, we examined the effect of CD30 ligand (CD30L) on CD30-positive H-RS and ALCL cells in long-term cultures or in primary cultures. CD30L induced various degrees of proliferation in three long-term cultured H-RS cell lines (L428, HDLM-2, and KM-H2) as well as in primary cultures of H-RS cells obtained directly from patients with Hodgkin's disease. In contrast, significant inhibition was observed in one of the ALCL cell lines (SU-DHL-1), but no growth inhibition or promotion in responding to exogenous CD30L was detected in three others (PB-1, JB-6, and McG-2), nor in primary cultures of ALCL cells. Expression of CD30L was determined by polymerase chain reaction in long-term cultured cells and by an immunohistochemical method in H-RS or ALCL cells de novo in tissue sections. None of the H-RS and ALCL cell lines was positive for CD30L. In tissue sections, we noticed that ALCL cells were generally CD30L-negative. In contrast, the anti-CD30L antibody reacted with a majority of H-RS cells with diffuse cytoplasmic staining. Most H-RS cells were CD30-positive, indicating co-expression of CD30 and CD30L in the majority of lymphoma cells. The persistent high levels of CD30 and CD30L expression in H-RS cells suggest that the autocrine CD30L-CD30 cytokine-receptor loop, in addition to having the paracrine activity previously thought to exist, could play important roles in the proliferation of H-RS cells. In contrast, the CD30L-mediated cytotoxicity may participate in the regression or slow progression of ALCL during the early phase of the disease in selected patients. However, when the disease progresses, the ALCL cells are likely to become resistant to exogenous CD30L. (Lab Invest 2000, 80:1111-1119.

CD30-mediated cell cycle arrest associated with induced expression of p21CIP1/WAF1 in the anaplastic large cell lymphoma cell line Karpas 299

“…CD30, as other members of the TNFR family, is able to promote cell survival as well as cell death (Duckett and Thompson, 1997;Amakawa et al, 1996). Previous studies have shown that activation of the CD30 receptor results in activation and enhanced proliferation of Hodgkin's lymphoma cells by activation of NF-kB (Lee et al, 1996(Lee et al, , 1997, but to induce an antiproliferative eect in anaplastic large cell lymphoma (ALCL) (HuÈ binger et al, 1999;Hsu and Hsu, 2000) and other CD30-positive cell lines, which has been described as induction of cell . Western blotting analysis was performed using whole cell lysate and anti-p53 or anti-actin antibody (b) Genomic DNA was extracted from JB6 and Karpas 299 cells and used for PCR ampli®cation of four genomic regions of p53 (exon 5, exon 6, exon 7, exon 8/9).…”

Aberrant expression of CD30 in neoplastic mast cells in high-grade mastocytosis

“…Such autocrine interactions via CD30 and its ligand have also been described in Hodgkin lymphoma. 45,46 Whether CD30 signaling in neoplastic mast cells, like in anaplastic large cell lymphoma cells, triggers NF-kB-mediated increased survival needs to be addressed in further functional studies. 47 The immunohistochemical and molecular demonstration of expression of CD30 by mast cells predominantly in the aggressive variants of mastocytosis may have important consequences for patients with this disease in several respects.…”

Clinical implications of the tumor necrosis factor family in benign and malignant hematologic disorders

“…23,24 CD30L has diverse biologic activity in different CD30ϩ cancers, ranging from enhancement of survival to no induction of apoptosis and cell cycle arrest. 14,[25][26][27][28][29] These paradoxical effects are caused by a differential effect on NF-B activation.…”