Polverini P J, Nickoloff B J
Department of Oral Medicine, University of Michigan School of Dentistry, Ann Arbor 48109-1078, USA.
Adv Cancer Res. 1995;66:235-53. doi: 10.1016/s0065-230x(08)60256-0.
Kaposi's sarcoma is a highly lethal tumor in patients with sexually acquired AIDS. A number of etiologic agents have been implicated in the development of this disease in this patient population and there is ample evidence that aberrant production of and responsiveness to KS tumor and host cell-derived cytokines plays a central role in the pathogenesis of AIDS-KS. In this review we propose that aberrant expression SF and c-met is central to the pathogenesis of KS. KS is a serious and life-threatening consequence for many patients with AIDS. Unfortunately, current therapeutic strategies for the treatment of this complex neoplasm have met with only limited success. In view of the poor survival rates for AIDS-KS patients which continue to decline at an alarming rate, it is eminently clear that a better understanding of the etiology and pathogenesis of this form of KS is needed if novel therapeutic strategies designed to successfully combat this disease are to be developed. If our hypothesis is validated, one could envision several approaches whereby the modulation of SF/c-met function or production might lead to a reduction in the incidence and severity of KS lesions. Antibody therapy directed against either SF-producing tumor cells or against the c-met receptor might decrease the incidence of new tumors by limiting their clonal expansion and lead to regression of established tumors by blocking SF-mediated tumor cell proliferation and neovascularization. It might also be possible to suppress production of SF or accessory cytokines involved in the induction SF production and thus short circuit SF/c-met growth-promoting effects. We have outlined a novel hypothesis for understanding the mechanism underlying the development of AIDS-associated KS. This is most certainly not the whole story, however. Clearly, other cytokines and alterations in natural host defenses and the immune system contribute significantly to the development of AIDS-associated KS. We believe, however, that recognition of SF/c-met as a participant in this disease is necessary if we are to more fully understand the pathogenesis of AIDS-associated KS.
卡波西肉瘤是性传播获得性艾滋病患者中一种高度致命的肿瘤。多种病因与该患者群体中这种疾病的发生有关，并且有充分证据表明，卡波西肉瘤肿瘤及宿主细胞衍生细胞因子的异常产生和反应在艾滋病相关卡波西肉瘤的发病机制中起核心作用。在本综述中，我们提出异常表达的SF和c - met是卡波西肉瘤发病机制的核心。对许多艾滋病患者来说，卡波西肉瘤是一种严重且危及生命的后果。不幸的是，目前针对这种复杂肿瘤的治疗策略仅取得了有限的成功。鉴于艾滋病相关卡波西肉瘤患者的生存率很低且仍在以惊人的速度下降，显然，如果要开发旨在成功对抗这种疾病的新治疗策略，就需要更好地了解这种形式的卡波西肉瘤的病因和发病机制。如果我们的假设得到验证，人们可以设想几种方法，通过调节SF/c - met的功能或产生，可能会降低卡波西肉瘤病变的发生率和严重程度。针对产生SF的肿瘤细胞或c - met受体的抗体疗法可能通过限制其克隆扩增来降低新肿瘤的发生率，并通过阻断SF介导的肿瘤细胞增殖和新血管形成导致已形成肿瘤的消退。也有可能抑制SF或参与诱导SF产生的辅助细胞因子的产生，从而消除SF/c - met的促生长作用。我们概述了一个关于理解艾滋病相关卡波西肉瘤发病机制的新假设。然而，这肯定不是全部情况。显然，其他细胞因子以及天然宿主防御和免疫系统的改变对艾滋病相关卡波西肉瘤的发展有重大贡献。然而，我们认为，如果我们要更全面地理解艾滋病相关卡波西肉瘤的发病机制，认识到SF/c - met是这种疾病的一个参与者是必要的。
