Naidu Y M, Rosen E M, Zitnick R, Goldberg I, Park M, Naujokas M, Polverini P J, Nickoloff B J
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5281-5. doi: 10.1073/pnas.91.12.5281.
Kaposi sarcoma (KS) is a complex multicellular neoplasm that is commonly associated with AIDS. The pathogenesis of KS is not well understood. KS tumor cells grow poorly in vitro and require medium conditioned by retrovirus-infected T lymphocytes. We observed that conditioned medium (CM) from type II human T-cell leukemia virus (HTLV-II)-infected T cells (HTLV-II CM) induces conversion of endothelial cells (ECs) to a KS tumor cell-like phenotype. ECs grown in HTLV-II CM acquired a spindle-shaped morphology, the ability to express factor XIIIa and other KS cell markers, and a cytokine production profile similar to that of KS cells. We found that HTLV-II CM contains large quantities of scatter factor (SF), an angiogenic cytokine that stimulates cell motility. SF induced ECs to become spindle-shaped and express factor XIIIa. Moreover, SF was found to be a mitogen for KS cells in vitro and was identified within KS lesions in vivo. SF mRNA was present in KS cells in vitro, and antibodies against SF inhibited the growth of KS cells. The receptor for SF, the c-met protein, was expressed by ECs, dermal dendrocytes, and KS tumor cells in vitro and in vivo. HTLV-II CM was highly angiogenic in vivo, which was blocked by antibodies against SF. Based on these findings, we suggest that SF plays a role in the initiation and maintenance of KS lesions.
卡波西肉瘤（KS）是一种复杂的多细胞肿瘤，通常与艾滋病相关。KS的发病机制尚不清楚。KS肿瘤细胞在体外生长不良，需要由逆转录病毒感染的T淋巴细胞条件培养基培养。我们观察到，来自II型人类T细胞白血病病毒（HTLV-II）感染的T细胞的条件培养基（HTLV-II CM）可诱导内皮细胞（ECs）转变为KS肿瘤细胞样表型。在HTLV-II CM中生长的ECs呈现纺锤形形态，能够表达因子XIIIa和其他KS细胞标志物，并且细胞因子产生谱与KS细胞相似。我们发现HTLV-II CM含有大量的散射因子（SF），一种刺激细胞运动的血管生成细胞因子。SF诱导ECs变成纺锤形并表达因子XIIIa。此外，SF在体外是KS细胞的促有丝分裂原，并且在体内KS病变中也被鉴定到。SF mRNA在体外的KS细胞中存在，并且针对SF的抗体抑制KS细胞的生长。SF的受体c-met蛋白在体外和体内的ECs、真皮树突状细胞和KS肿瘤细胞中均有表达。HTLV-II CM在体内具有高度血管生成性，这被针对SF的抗体所阻断。基于这些发现，我们认为SF在KS病变的起始和维持中起作用。
