Insogna K L
Yale University School of Medicine, New Haven, Connecticut.
Endocrinol Metab Clin North Am. 1989 Sep;18(3):779-94.
Humoral hypercalcemia of malignancy is a common cause of malignancy-associated hypercalcemia. This syndrome is caused by the elaboration of a tumor-derived factor or factors that induce intense bone resorption and increased renal tubular calcium reabsorption. Recently, the PTHrP has been isolated from tumors associated with HHM, and a single copy gene directing its synthesis has been identified on human chromosome 12. Analysis of mRNA from tumor-derived tissue suggests a complex pattern of hybridizing transcripts, implicating alternative processing of this gene. However, the circulating form or forms of the protein have yet to be determined. Synthetic amino-terminal polypeptides of PTHrP in vivo and in vitro reproduce all of the essential features of HHM. Preliminary studies suggest that neutralizing antisera to this protein reverse the hypercalcemia in experimental models for HHM. Thus, it appears likely that this protein has a central pathogenic role in HHM. The development of antisera to this protein will aid in the detection and diagnosis of malignancy-associated hypercalcemia. Antagonists to this molecule may be helpful in treating this disorder.
恶性肿瘤体液性高钙血症是恶性肿瘤相关性高钙血症的常见原因。该综合征由肿瘤分泌一种或多种因子引起，这些因子可导致强烈的骨吸收和肾小管钙重吸收增加。最近，已从与恶性肿瘤体液性高钙血症相关的肿瘤中分离出甲状旁腺激素相关蛋白（PTHrP），并在人类12号染色体上鉴定出指导其合成的单拷贝基因。对肿瘤来源组织的mRNA分析表明存在复杂的杂交转录本模式，提示该基因存在可变加工。然而，该蛋白的循环形式尚未确定。PTHrP的合成氨基末端多肽在体内和体外重现了恶性肿瘤体液性高钙血症的所有基本特征。初步研究表明，针对该蛋白的中和抗血清可逆转恶性肿瘤体液性高钙血症实验模型中的高钙血症。因此，该蛋白似乎在恶性肿瘤体液性高钙血症中具有核心致病作用。针对该蛋白的抗血清的开发将有助于检测和诊断恶性肿瘤相关性高钙血症。该分子的拮抗剂可能有助于治疗这种疾病。
