Autocrine growth regulation of CD30 ligand in CD30-expressing Reed-Sternberg cells: distinction between Hodgkin's disease and anaplastic large cell lymphoma.
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.
Hsu
P L
PL
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, USA. smhsu@ha.mc.ntu.edu.tw
Hsu
S M
SM
D000818:Animals; D019898:Autocrine Communication; D053285:CD30 Ligand; D019556:COS Cells; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D003937:Diagnosis, Differential; D006689:Hodgkin Disease / Q000473:pathology*; D006801:Humans; D017730:Ki-1 Antigen / Q000378:metabolism*; D017728:Lymphoma, Large-Cell, Anaplastic / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D016539:Reed-Sternberg Cells / Q000378:metabolism* / Q000473:pathology*
D053285:CD30 Ligand; D017730:Ki-1 Antigen; D008562:Membrane Glycoproteins; C505774:TNFSF8 protein, human