Mills G B, May C, Hill M, Campbell S, Shaw P, Marks A
Oncology Research, Toronto General Hospital, Ontario, Canada.
J Clin Invest. 1990 Sep;86(3):851-5. doi: 10.1172/JCI114784.
Human ovarian cancer, the leading cause of death from gynecologic malignancy, tends to remain localized to the peritoneal cavity until late in the disease. In established disease, ascitic fluid accumulates in the peritoneal cavity. We have previously demonstrated that this ascitic fluid is a potent source of in vitro mitogenic activity including at least one unique growth factor. We now report that the human ovarian adenocarcinoma line, HEY, can be induced to grow intraperitoneally in immunodeficient nude mice in the presence (23/28 mice), but not absence (0/21 mice) of ascitic fluid from ovarian cancer patients. Ascitic fluid from patients with benign disease did not have similar effects on intraperitoneal growth of HEY cells (1/15 mice). Once tumors were established by injections of exogenous ascitic fluid, they could progress in the absence of additional injections of ascitic fluid. The mice eventually developed ascitic fluid which contained potent growth factor activity, suggesting that the tumors eventually produced autologous growth factors. This nude mouse model provides a system to study the action of ovarian cancer growth factors on tumor growth in vivo and to evaluate preclinically, therapeutic approaches designed to counteract the activity of these growth factors.
人类卵巢癌是妇科恶性肿瘤死亡的主要原因,在疾病晚期之前往往局限于腹腔。在疾病确诊时,腹腔内会积聚腹水。我们之前已经证明,这种腹水是体外促有丝分裂活性的强大来源,其中包括至少一种独特的生长因子。我们现在报告,人卵巢腺癌细胞系HEY在有(23/28只小鼠)而非无(0/21只小鼠)卵巢癌患者腹水的情况下,可被诱导在免疫缺陷裸鼠体内腹腔生长。良性疾病患者的腹水对HEY细胞的腹腔生长没有类似作用(1/15只小鼠)。一旦通过注射外源性腹水形成肿瘤,在不额外注射腹水的情况下它们也能进展。小鼠最终会产生含有强大生长因子活性的腹水,这表明肿瘤最终产生了自身生长因子。这种裸鼠模型提供了一个系统,用于研究卵巢癌生长因子在体内对肿瘤生长的作用,并在临床前评估旨在对抗这些生长因子活性的治疗方法。