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Studies on the mechanism of leucocytosis and hypercalcemia associated with head and neck cancer

白细胞增多和高钙血症与头颈癌相关的机制研究

基本信息

批准号：
02454457
负责人：
SAKUDA Masayoshi
金额：
$ 3.52万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-02454457/
关键词：
Head and Neck Cancer leucocytosis hypercalcemia paraneoplastic Syndrome 頭頸部癌

项目摘要

In this studies, the mechanism underlying leucocytosis and hypercalcemia associated with malignancy was investigated.In this investigation of leucocytosis and/or hypercalcemia occasionally occurred in patients with oral malignancies, some patients have only one of them, whereas others have both. These results demonstrate that these paraneoplastic syndromes result from different mechanisms.In accordance with this fact, tongue cancer of a patient with hypercalcemia was inoculated into nude mice and, at the same time, cultured in vitro. These tumor cells secrete high level of PGE_2, which is revealefl, to play important roles in bone resorption. Furthermore, high level of PGE_2 or Ca^<2+> in culture medium promoted DNA synthesis of tumor cells. In the further studies used VX_2 cancer cells, the cells secreted PGE_2 and also parathyroid hormone-related protein (PTHrP). These humoral factors are involved in pathogenesis of hypercalcemia. Increase of serum PGEP_2 and PTHrP results in enlargement of bone marrow cavity of parietal bone. Administration of indomethacin or antagonist of PTHRP, PTHRP analogue, prevented a bone resorbing activity of these factors. Both PGE_2 and PTHRP promoted Vxg cell growth as autocrine growth factors. Stimulation of VX_2 cell proliferation by PGE_2 or ETHRP was closely correlated with a transient elevation of intracellular free Ca^<2+> by influx of extracellular free Ca^<2+>.It is, therefore, suggested that induction of the hypercalcemia is an essential event for VX_2 cells to maintain an environment which favors their autonomous growth.

本研究探讨了口腔恶性肿瘤患者白细胞增多和高钙血症的发病机制。在对口腔恶性肿瘤患者偶尔出现的白细胞增多和/或高钙血症的研究中，一些患者只有一种，而另一些患者两种情况都有。这些结果表明，这些副肿瘤综合征是由不同的机制引起的。根据这一事实，将一名高钙血症患者的舌癌接种到裸鼠体内，同时进行体外培养。这些肿瘤细胞分泌高水平的前列腺素E_2，在骨吸收中发挥重要作用。此外，高浓度的PGE_2或Ca~(2+)促进肿瘤细胞的DNA合成。在使用VX_2癌细胞的进一步研究中，该细胞分泌PGE_2和甲状旁腺激素相关蛋白(PTHrP)。这些体液因子参与了高钙血症的发病机制。血清PGEP_2、PTHrP升高可导致顶骨骨髓腔扩大。给予消炎痛或PTHrP的拮抗剂，PTHrP类似物，可阻止这些因子的骨吸收活性。PGE2和PTHrP均作为自分泌生长因子促进Vxg细胞生长。PGE_2或ETHRP对VX_2细胞增殖的刺激作用与细胞外游离Ca~(2+)的瞬时升高密切相关。因此，提示诱导高钙血症是VX_2细胞维持自主生长环境的重要事件。