RELATIONSHIP BETWEEN BONE RESORBING ACTIVITY & COLONY

实体瘤常常与骨量增加有关。 吸收和高钙血症。骨量增加的机制 吸收是由肿瘤细胞产生的体液因子或 刺激破骨细胞性骨吸收的因素。最近， 我们和其他人注意到口腔肿瘤 因为高钙血症通常与白细胞增多有关， 伴随着菌落刺激活性的产生。 为了找出高血钙症的致病因素 这些肿瘤，我们的方法将是使用体外生物测定 骨吸收的基础上释放先前纳入的 45Ca在器官培养中表征骨吸收因子的研究 存在于肿瘤细胞培养液中，并确定 这些因子与肿瘤产物的关系 负责刺激集落形成的白细胞增多症 小鼠骨髓单个核细胞在甲基介质中的培养 纤维素。我们计划评估骨骼之间的关系 再吸收活性和菌落刺激活性 来自患者的肿瘤细胞的培养液 仅表现为上颌骨鳞状细胞癌 白血球增多症，来自鳞癌患者 仅表现为高钙血症的上颌骨，以及一名患者 舌鳞状细胞癌患者同时表现为 高钙血症和白细胞增多症。这些肿瘤已经携带了 在裸鼠身上，初步结果表明只有那些 与菌落刺激活动相关的生产原因 白细胞增多症，只有与骨吸收相关的 活动的产生会导致高钙血症。由于单元格派生 从这些肿瘤现在保持在培养中，我们计划 进一步纯化骨吸收活性和菌落 刺激这些肿瘤产生的活性，并决定 菌落刺激活性与已知菌落的关系 刺激因子(CSF)。我们希望这些研究能够 阐明肿瘤细胞增加破骨细胞的机制 骨吸收并引起白细胞增多，并可能导致 影响破骨细胞的正常因素鉴定 骨吸收和白细胞分化。

Solid tumors are frequently associated with increased bone resorption and hypercalcenia. The mechanism for increased bone resorption is production by the tumor cells of a humoral factor or factors which stimulate osteoclastic bone resorption. Recently, we and others have noted that tumors of the oral cavity which cause hypercalcenia are often associated with leukocytosis, concomitantly with the production of colony stimulating activity. In order to identify the factors responsible for hypercalcemia in these tumors, our approach will be to use an in vitro bioassay for bone resorption based on the release of previously incorporated 45Ca in organ culture to characterize the bone resorbing factors present in the tumor cell culture media, and determine the relationship between these factors and the tumor products responsible for leukocytosis which stimulate colony formation in cultures of mouse bone marrow mononuclear cells in methyl cellulose. We plan to evaluate the relationships between bone resorbing activity and colony stimulating activity by examining culture media from tumor cells derived from a patient with squamous cell carcinoma of the maxilla who manifested only leukocytosis, from a patient with squamous cell carcinoma of the maxilla who manifested only hypercalcemia, and from a patient with squamous cell carcinoma of the tongue who manifested both hypercalcemia and leukocytosis. These tumors have been carried in nude mice and preliminary results show that only those associated with colony stimulating activity production cause leukocytosis, and only those associated with bone resorbing activity production cause hypercalcemia. Since cells derived from these tumors are now maintained in culture, we plan to purify further the bone resorbing activity and the colony stimulating activity produced by these tumors, and determine the relationship of the colony stimulating activity to known colony stimulating factors (CSFs). Our hope is that these studies will clarify the mechanisms by which tumor cells increase osteoclastic bone resorption and cause leukocytosis, and may lead to identification of normal factors which influence both osteoclastic bone resorption and leukocyte differentiation.