Hodgkin and Reed-Sternberg cells express functional c-kit receptors and interact with primary fibroblasts from Hodgkin's disease-involved lymph nodes through soluble and membrane-bound stem cell factor

被引:21
作者
Aldinucci, D
Poletto, D
Nanni, P
Degan, M
Gloghini, A
Di Francia, R
Russo, S
Carbone, A
Pinto, A
Gattei, V
机构
[1] Ist Nazl Tumori, IRCCS, Ctr Riferimento Oncol, Clin & Expt Haematol Res Unit, I-33081 Aviano, Italy
[2] Ist Nazl Tumori, IRCCS, Ctr Riferimento Oncol, Div Pathol, Aviano, Italy
关键词
Hodgkin cells; Reed-Sternberg cells; c-kit; stem cell factor; cytokine receptors;
D O I
10.1046/j.1365-2141.2002.03732.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Classic Hodgkin's disease (cHD) is a lymphoid neoplasia characterized by few malignant Hodgkin and Reed-Sternberg (H-RS) cells, embedded in an abundant background of non-tumour cells. We have previously demonstrated the expression in primary H-RS cells of the receptor tyrosine kinase (RTK) c-kit; here we describe its functional role in the cross-talk between H-RS cells themselves with neighbouring cell populations. In particular, we analysed the expression of c-kit and its ligand stem cell factor (SCF) in a panel of HD-derived cell lines and fibroblasts from HD-involved lymph nodes (HDF). While c-kit was expressed by HD-derived cell lines, usually in the absence of SCF, this latter molecule, in its soluble and/or membrane-bound (mb) form, was in turn expressed at a high level by primary HDF. In vitro adhesion between HD-derived cell lines and HDF was mainly mediated by c-kit/SCF interactions, and this phenomenon was significantly inhibited by an excess of soluble SCF or by neutralizing anti-c-kit monoclonal antibodies. Furthermore, both soluble and mb-SCF increased growth and colony survival of HD-derived cell lines; these effects were significantly enhanced upon co-stimulation of H-RS cells with interleukin 9. Finally, soluble SCF was able to partially rescue H-RS cells from apoptosis induced by serum starvation. Taken together, our data indicated the expression of functional c-kit receptor by H-RS cells and suggests a role of SCF in the pathobiology of cHD.
引用
收藏
页码:1055 / 1064
页数:10
相关论文
共 54 条
  • [21] Harris NL, 1999, MODERN PATHOL, V12, P159
  • [22] HARRIS NL, 1994, BLOOD, V84, P1361
  • [23] Human peripheral blood eosinophils express stem cell factor
    Hartman, ML
    Piliponsky, AM
    Temkin, V
    Levi-Schaffer, F
    [J]. BLOOD, 2001, 97 (04) : 1086 - 1091
  • [24] Hodgkin/Reed-Sternberg cells induce fibroblasts to secrete eotaxin, a potent chemoattractant for T cells and eosinophils
    Jundt, F
    Anagnostopoulos, I
    Bommert, K
    Emmerich, F
    Müller, G
    Foss, HD
    Royer, HD
    Stein, H
    Dörken, B
    [J]. BLOOD, 1999, 94 (06) : 2065 - 2071
  • [25] Kadin Marshall E., 1994, Current Opinion in Oncology, V6, P456, DOI 10.1097/00001622-199409000-00002
  • [26] Interleukin 13 is secreted by and stimulates the growth of Hodgkin and Reed-Sternberg cells
    Kapp, U
    Yeh, WC
    Patterson, B
    Elia, AJ
    Kägi, D
    Ho, A
    Hessel, A
    Tipsword, M
    Williams, A
    Mirtsos, C
    Itie, A
    Moyle, M
    Mak, TW
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (12) : 1939 - 1945
  • [27] Krystal GW, 1996, CANCER RES, V56, P370
  • [28] LAHM H, 1995, CELL GROWTH DIFFER, V6, P1111
  • [29] The metastatic ability of Ewing's sarcoma cells is modulated by stem cell factor and by its receptor c-kit
    Landuzzi, L
    De Giovanni, C
    Nicoletti, G
    Rossi, I
    Ricci, C
    Astolfi, A
    Scopece, L
    Scotlandi, K
    Serra, M
    Bagnara, GP
    Nanni, P
    Lollini, PL
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2000, 157 (06) : 2123 - 2131
  • [30] Landuzzi L, 1998, INT J CANCER, V78, P441, DOI 10.1002/(SICI)1097-0215(19981109)78:4<441::AID-IJC9>3.3.CO