Castle V, Varani J, Fligiel S, Prochownik E V, Dixit V
Department of Pediatrics, University of Michigan, Ann Arbor 48109.
J Clin Invest. 1991 Jun;87(6):1883-8. doi: 10.1172/JCI115212.
Thrombospondin (TSP) is a trimeric glycoprotein which is synthesized and incorporated into the extracellular matrix by a wide variety of cells. TSP is involved in a number of cellular processes which govern tumor cell behavior including mitogenesis, attachment, migration, and differentiation. To directly assess the role of TSP in tumor cell growth and spread, a human squamous carcinoma cell line, with high TSP production and an invasive phenotype, was transfected with a TSP cDNA antisense expression vector. Five unique transfected clones were obtained with reduced TSP production. Expression of the transfected antisense sequence in these clones was verified by a ribonuclease protection assay. These clones demonstrated reduced growth rates in vitro when compared with a vector transfected control. After subcutaneous inoculation into athymic mice, the antisense clones formed either no tumors or tumors that were slow growing and highly differentiated. This contrasted with the vector-transfected clone which produced poorly differentiated, rapidly growing, invasive tumors. Our results argue in favor of a direct role for TSP in determining the malignant phenotype of certain human tumors.
血小板反应蛋白（TSP）是一种三聚体糖蛋白，由多种细胞合成并整合到细胞外基质中。TSP参与了许多调控肿瘤细胞行为的细胞过程，包括有丝分裂、黏附、迁移和分化。为了直接评估TSP在肿瘤细胞生长和扩散中的作用，将一个高表达TSP且具有侵袭表型的人鳞状癌细胞系用TSP cDNA反义表达载体进行转染。获得了五个TSP表达降低的独特转染克隆。通过核糖核酸酶保护试验验证了这些克隆中转染的反义序列的表达。与载体转染的对照相比，这些克隆在体外显示出降低的生长速率。皮下接种到无胸腺小鼠后，反义克隆要么不形成肿瘤，要么形成生长缓慢且高度分化的肿瘤。这与载体转染的克隆形成鲜明对比，载体转染的克隆产生低分化、快速生长的侵袭性肿瘤。我们的结果支持TSP在决定某些人类肿瘤的恶性表型中起直接作用。
